The variant NM_000548.5:c.1019_1022dup p.(Ile342Cysfs*10), detected in heterozygosity in the TSC2 gene, has not been described in the literature nor in gnomAD at the time of this submission. This is a frameshift variant that introduces a premature stop codon, which is predicted to lead to the creation of a truncated protein and/or a reduction of its expression by mRNA degradation. Aditionally, the proband has several differential phenotypes for this entity (West syndrome, cardiac rhabdomyomas, hypochromic skin patches, bilateral angiomyolipomas, etc). With the available information, this variant is classified as pathogenic with the following ACMG codes: PM2_supp, PVS1, PP4_strong.
ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.1019_1022dup (p.Ile342fs)
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.
(1)
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.
Pathogenic
1
no assertion criteria provided
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000548.5(TSC2):c.1019_1022dup (p.Ile342fs)
Variation ID: 3370394 Accession: VCV003370394.1
- Type and length
-
Duplication, 4 bp
- Location
-
Cytogenetic: 16p13.3 16: 2060711-2060712 (GRCh38) [ NCBI UCSC ] 16: 2110712-2110713 (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 Nov 3, 2024 Nov 3, 2024 Oct 31, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000548.5:c.1019_1022dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Ile342fs frameshift NM_001077183.3:c.1019_1022dup NP_001070651.1:p.Ile342fs frameshift NM_001114382.3:c.1019_1022dup NP_001107854.1:p.Ile342fs frameshift NM_001318827.2:c.908_911dup NP_001305756.1:p.Ile305fs frameshift NM_001318829.2:c.872_875dup NP_001305758.1:p.Ile293fs frameshift NM_001318831.2:c.419_422dup NP_001305760.1:p.Ile142fs frameshift NM_001318832.2:c.1052_1055dup NP_001305761.1:p.Ile353fs frameshift NM_001363528.2:c.1019_1022dup NP_001350457.1:p.Ile342fs frameshift NM_001370404.1:c.1019_1022dup NP_001357333.1:p.Ile342fs frameshift NM_001370405.1:c.1019_1022dup NP_001357334.1:p.Ile342fs frameshift NM_001406663.1:c.1019_1022dup NP_001393592.1:p.Ile342fs frameshift NM_001406664.1:c.1019_1022dup NP_001393593.1:p.Ile342fs frameshift NM_001406665.1:c.1019_1022dup NP_001393594.1:p.Ile342fs frameshift NM_001406667.1:c.1109_1112dup NP_001393596.1:p.Ile372fs frameshift NM_001406668.1:c.1109_1112dup NP_001393597.1:p.Ile372fs frameshift NM_001406670.1:c.908_911dup NP_001393599.1:p.Ile305fs frameshift NM_001406671.1:c.1007_1010dup NP_001393600.1:p.Ile338fs frameshift NM_001406673.1:c.1007_1010dup NP_001393602.1:p.Ile338fs frameshift NM_001406675.1:c.872_875dup NP_001393604.1:p.Ile293fs frameshift NM_001406676.1:c.872_875dup NP_001393605.1:p.Ile293fs frameshift NM_001406677.1:c.962_965dup NP_001393606.1:p.Ile323fs frameshift NM_001406678.1:c.908_911dup NP_001393607.1:p.Ile305fs frameshift NM_001406679.1:c.872_875dup NP_001393608.1:p.Ile293fs frameshift NM_001406680.1:c.419_422dup NP_001393609.1:p.Ile142fs frameshift NM_001406681.1:c.557_560dup NP_001393610.1:p.Ile188fs frameshift NM_001406682.1:c.419_422dup NP_001393611.1:p.Ile142fs frameshift NM_001406683.1:c.419_422dup NP_001393612.1:p.Ile142fs frameshift NM_001406684.1:c.419_422dup NP_001393613.1:p.Ile142fs frameshift NM_001406685.1:c.419_422dup NP_001393614.1:p.Ile142fs frameshift NM_001406686.1:c.419_422dup NP_001393615.1:p.Ile142fs frameshift NM_001406687.1:c.419_422dup NP_001393616.1:p.Ile142fs frameshift NM_001406688.1:c.419_422dup NP_001393617.1:p.Ile142fs frameshift NM_001406689.1:c.-413_-410dup 5 prime UTR NM_001406690.1:c.-413_-410dup 5 prime UTR NM_001406691.1:c.-413_-410dup 5 prime UTR NM_001406692.1:c.-413_-410dup 5 prime UTR NM_001406693.1:c.-413_-410dup 5 prime UTR NM_001406694.1:c.-294_-291dup 5 prime UTR NM_001406695.1:c.-294_-291dup 5 prime UTR NM_001406696.1:c.-413_-410dup 5 prime UTR NM_001406697.1:c.-413_-410dup 5 prime UTR NM_001406698.1:c.-589_-586dup 5 prime UTR NM_021055.3:c.1019_1022dup NP_066399.2:p.Ile342fs frameshift NR_176225.1:n.1129_1132dup non-coding transcript variant NR_176226.1:n.1129_1132dup non-coding transcript variant NR_176227.1:n.1129_1132dup non-coding transcript variant NR_176228.1:n.1129_1132dup non-coding transcript variant NR_176229.1:n.1129_1132dup non-coding transcript variant NC_000016.10:g.2060713_2060716dup NC_000016.9:g.2110714_2110717dup NG_005895.1:g.16408_16411dup LRG_487:g.16408_16411dup LRG_487t1:c.1019_1022dup LRG_487p1:p.Ile342Valfs - Protein change
- I142fs, I188fs, I293fs, I305fs, I323fs, I338fs, I342fs, I353fs, I372fs
- Other names
- -
- Canonical SPDI
- NC_000016.10:2060711:CTGTC:CTGTCTGTC
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- 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. |
|||
| TSC2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
10758 | 10957 | |
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. |
|---|---|---|---|---|
| Pathogenic (1) |
no assertion criteria provided
|
Oct 31, 2024 | RCV004776423.1 |
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. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Oct 31, 2024)
|
no assertion criteria provided
Method: clinical testing
|
Tuberous sclerosis 2
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
unknown
|
CGC Genetics, Unilabs
Accession: SCV005387586.1
First in ClinVar: Nov 03, 2024 Last updated: Nov 03, 2024 |
Comment:
The variant NM_000548.5:c.1019_1022dup p.(Ile342Cysfs*10), detected in heterozygosity in the TSC2 gene, has not been described in the literature nor in gnomAD at the time of … (more)
The variant NM_000548.5:c.1019_1022dup p.(Ile342Cysfs*10), detected in heterozygosity in the TSC2 gene, has not been described in the literature nor in gnomAD at the time of this submission. This is a frameshift variant that introduces a premature stop codon, which is predicted to lead to the creation of a truncated protein and/or a reduction of its expression by mRNA degradation. Aditionally, the proband has several differential phenotypes for this entity (West syndrome, cardiac rhabdomyomas, hypochromic skin patches, bilateral angiomyolipomas, etc). With the available information, this variant is classified as pathogenic with the following ACMG codes: PM2_supp, PVS1, PP4_strong. (less)
Sex: male
|
Comment:
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 variant NM_000548.5:c.1019_1022dup p.(Ile342Cysfs*10), detected in heterozygosity in the TSC2 gene, has not been described in the literature nor in gnomAD at the time of this submission. This is a frameshift variant that introduces a premature stop codon, which is predicted to lead to the creation of a truncated protein and/or a reduction of its expression by mRNA degradation. Aditionally, the proband has several differential phenotypes for this entity (West syndrome, cardiac rhabdomyomas, hypochromic skin patches, bilateral angiomyolipomas, etc). With the available information, this variant is classified as pathogenic with the following ACMG codes: PM2_supp, PVS1, PP4_strong.
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated Nov 10, 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.