The c.59_61dupCGC variant has not, to our knowledge, been published in the literature as pathogenic or benign. This in-frame duplication of three nucleotides in occurs in a region that is not conserved and is not located in a known functional domain. Since in-frame duplications may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time and we consider c.59_61dupCGC to be a variant of uncertain significance.
ClinVar Genomic variation as it relates to human health
NM_020975.6(RET):c.59_61dup (p.Pro20_Leu21insPro)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(4)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Uncertain significance
4
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_020975.6(RET):c.59_61dup (p.Pro20_Leu21insPro)
Variation ID: 423618 Accession: VCV000423618.13
- Type and length
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Duplication, 3 bp
- Location
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Cytogenetic: 10q11.21 10: 43077314-43077315 (GRCh38) [ NCBI UCSC ] 10: 43572762-43572763 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 29, 2017 May 1, 2024 Feb 5, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_020975.6:c.59_61dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_066124.1:p.Pro20_Leu21insPro inframe insertion NM_000323.2:c.59_61dup NP_000314.1:p.Pro20_Leu21insPro inframe indel NM_001406743.1:c.59_61dup NP_001393672.1:p.Pro20_Leu21insPro inframe indel NM_001406744.1:c.59_61dup NP_001393673.1:p.Pro20_Leu21insPro inframe indel NM_001406759.1:c.59_61dup NP_001393688.1:p.Pro20_Leu21insPro inframe indel NM_001406760.1:c.59_61dup NP_001393689.1:p.Pro20_Leu21insPro inframe indel NM_001406761.1:c.59_61dup NP_001393690.1:p.Pro20_Leu21insPro inframe indel NM_001406762.1:c.59_61dup NP_001393691.1:p.Pro20_Leu21insPro inframe indel NM_001406763.1:c.59_61dup NP_001393692.1:p.Pro20_Leu21insPro inframe indel NM_001406764.1:c.59_61dup NP_001393693.1:p.Pro20_Leu21insPro inframe indel NM_001406765.1:c.59_61dup NP_001393694.1:p.Pro20_Leu21insPro inframe indel NM_001406766.1:c.59_61dup NP_001393695.1:p.Pro20_Leu21insPro inframe indel NM_001406767.1:c.59_61dup NP_001393696.1:p.Pro20_Leu21insPro inframe indel NM_001406768.1:c.59_61dup NP_001393697.1:p.Pro20_Leu21insPro inframe indel NM_001406769.1:c.59_61dup NP_001393698.1:p.Pro20_Leu21insPro inframe indel NM_001406770.1:c.59_61dup NP_001393699.1:p.Pro20_Leu21insPro inframe indel NM_001406771.1:c.59_61dup NP_001393700.1:p.Pro20_Leu21insPro inframe indel NM_001406772.1:c.59_61dup NP_001393701.1:p.Pro20_Leu21insPro inframe indel NM_001406773.1:c.59_61dup NP_001393702.1:p.Pro20_Leu21insPro inframe indel NM_001406774.1:c.59_61dup NP_001393703.1:p.Pro20_Leu21insPro inframe indel NM_001406775.1:c.59_61dup NP_001393704.1:p.Pro20_Leu21insPro inframe indel NM_001406776.1:c.59_61dup NP_001393705.1:p.Pro20_Leu21insPro inframe indel NM_001406777.1:c.59_61dup NP_001393706.1:p.Pro20_Leu21insPro inframe indel NM_001406778.1:c.59_61dup NP_001393707.1:p.Pro20_Leu21insPro inframe indel NM_001406779.1:c.59_61dup NP_001393708.1:p.Pro20_Leu21insPro inframe indel NM_001406780.1:c.59_61dup NP_001393709.1:p.Pro20_Leu21insPro inframe indel NM_001406781.1:c.59_61dup NP_001393710.1:p.Pro20_Leu21insPro inframe indel NM_001406782.1:c.59_61dup NP_001393711.1:p.Pro20_Leu21insPro inframe indel NM_001406783.1:c.59_61dup NP_001393712.1:p.Pro20_Leu21insPro inframe indel NM_001406784.1:c.59_61dup NP_001393713.1:p.Pro20_Leu21insPro inframe indel NM_001406785.1:c.59_61dup NP_001393714.1:p.Pro20_Leu21insPro inframe indel NM_001406786.1:c.59_61dup NP_001393715.1:p.Pro20_Leu21insPro inframe indel NM_001406787.1:c.59_61dup NP_001393716.1:p.Pro20_Leu21insPro inframe indel NM_001406788.1:c.59_61dup NP_001393717.1:p.Pro20_Leu21insPro inframe indel NM_001406789.1:c.59_61dup NP_001393718.1:p.Pro20_Leu21insPro inframe indel NM_001406790.1:c.59_61dup NP_001393719.1:p.Pro20_Leu21insPro inframe indel NM_001406791.1:c.59_61dup NP_001393720.1:p.Pro20_Leu21insPro inframe indel NM_001406792.1:c.59_61dup NP_001393721.1:p.Pro20_Leu21insPro inframe indel NM_001406793.1:c.59_61dup NP_001393722.1:p.Pro20_Leu21insPro inframe indel NM_001406794.1:c.59_61dup NP_001393723.1:p.Pro20_Leu21insPro inframe indel NM_020629.2:c.59_61dup NP_065680.1:p.Pro20_Leu21insPro inframe indel NM_020630.7:c.59_61dup NP_065681.1:p.Pro20_Leu21insPro inframe indel NM_020975.4:c.59_61dupCGC inframe indel NC_000010.11:g.43077317_43077319dup NC_000010.10:g.43572765_43572767dup NG_007489.1:g.5249_5251dup NG_045003.1:g.4504_4506dup LRG_518:g.5249_5251dup LRG_518t1:c.59_61dup LRG_518p1:p.Pro20_Leu21insPro LRG_518t2:c.59_61dup LRG_518p2:p.Pro20_Leu21insPro - Protein change
- -
- Other names
- -
- Canonical SPDI
- NC_000010.11:43077314:GCCGC:GCCGCCGC
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| RET | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
3598 | 3720 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
|
Feb 14, 2017 | RCV000479274.3 | |
| Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
|
Feb 5, 2024 | RCV000541134.12 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
May 24, 2022 | RCV002356788.2 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(Feb 14, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000573336.3
First in ClinVar: Apr 29, 2017 Last updated: Apr 29, 2017 |
Comment:
The c.59_61dupCGC variant has not, to our knowledge, been published in the literature as pathogenic or benign. This in-frame duplication of three nucleotides in occurs … (more)
The c.59_61dupCGC variant has not, to our knowledge, been published in the literature as pathogenic or benign. This in-frame duplication of three nucleotides in occurs in a region that is not conserved and is not located in a known functional domain. Since in-frame duplications may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time and we consider c.59_61dupCGC to be a variant of uncertain significance. (less)
|
|
|
Uncertain significance
(Jan 07, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Multiple endocrine neoplasia, type 2
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000658489.7
First in ClinVar: Dec 26, 2017 Last updated: Feb 28, 2024 |
Comment:
This variant, c.59_61dup, results in the insertion of 1 amino acid(s) of the RET protein (p.Pro20dup), but otherwise preserves the integrity of the reading frame. … (more)
This variant, c.59_61dup, results in the insertion of 1 amino acid(s) of the RET protein (p.Pro20dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with RET-related conditions. ClinVar contains an entry for this variant (Variation ID: 423618). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
|
|
|
Uncertain significance
(May 24, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002653657.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.59_61dupCGC variant (also known as p.P20dup), located in coding exon 1 of the RET gene, results from an in-frame duplication of CGC at nucleotide … (more)
The c.59_61dupCGC variant (also known as p.P20dup), located in coding exon 1 of the RET gene, results from an in-frame duplication of CGC at nucleotide positions 59 to 61. This results in the duplication of an extra proline residue between codons 20 and 21. This amino acid position is well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
|
|
|
Uncertain Significance
(Feb 05, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Multiple endocrine neoplasia, type 2
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004834586.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Comment:
This variant causes an in-frame insertion of one amino acid in the RET protein. To our knowledge, functional studies have not been reported for this … (more)
This variant causes an in-frame insertion of one amino acid in the RET protein. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 32091409). This variant has been identified in 6/142268 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
Number of individuals with the variant: 1
|
Comment:
Comment:
This variant, c.59_61dup, results in the insertion of 1 amino acid(s) of the RET protein (p.Pro20dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with RET-related conditions. ClinVar contains an entry for this variant (Variation ID: 423618). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Comment:
The c.59_61dupCGC variant (also known as p.P20dup), located in coding exon 1 of the RET gene, results from an in-frame duplication of CGC at nucleotide positions 59 to 61. This results in the duplication of an extra proline residue between codons 20 and 21. This amino acid position is well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Comment:
This variant causes an in-frame insertion of one amino acid in the RET protein. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 32091409). This variant has been identified in 6/142268 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
The c.59_61dupCGC variant has not, to our knowledge, been published in the literature as pathogenic or benign. This in-frame duplication of three nucleotides in occurs in a region that is not conserved and is not located in a known functional domain. Since in-frame duplications may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time and we consider c.59_61dupCGC to be a variant of uncertain significance.
Comment:
This variant, c.59_61dup, results in the insertion of 1 amino acid(s) of the RET protein (p.Pro20dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with RET-related conditions. ClinVar contains an entry for this variant (Variation ID: 423618). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Comment:
The c.59_61dupCGC variant (also known as p.P20dup), located in coding exon 1 of the RET gene, results from an in-frame duplication of CGC at nucleotide positions 59 to 61. This results in the duplication of an extra proline residue between codons 20 and 21. This amino acid position is well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Comment:
This variant causes an in-frame insertion of one amino acid in the RET protein. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 32091409). This variant has been identified in 6/142268 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Comparison of BRCA versus non-BRCA germline mutations and associated somatic mutation profiles in patients with unselected breast cancer. | Chen B | Aging | 2020 | PMID: 32091409 |
Text-mined citations for rs1064796534 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Sep 29, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.