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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TSC2 protein function. This variant has not been reported in the literature in individuals affected with TSC2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1634 of the TSC2 protein (p.Arg1634Gly).
ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.4900C>G (p.Arg1634Gly)
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.
Uncertain significance
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000548.5(TSC2):c.4900C>G (p.Arg1634Gly)
Variation ID: 2997322 Accession: VCV002997322.1
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 16p13.3 16: 2086782 (GRCh38) [ NCBI UCSC ] 16: 2136783 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Feb 29, 2024 Feb 28, 2024 Jun 29, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000548.5:c.4900C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Arg1634Gly missense NM_001077183.3:c.4699C>G NP_001070651.1:p.Arg1567Gly missense NM_001114382.3:c.4831C>G NP_001107854.1:p.Arg1611Gly missense NM_001318827.2:c.4591C>G NP_001305756.1:p.Arg1531Gly missense NM_001318829.2:c.4555C>G NP_001305758.1:p.Arg1519Gly missense NM_001318831.2:c.4168C>G NP_001305760.1:p.Arg1390Gly missense NM_001318832.2:c.4732C>G NP_001305761.1:p.Arg1578Gly missense NM_001363528.2:c.4702C>G NP_001350457.1:p.Arg1568Gly missense NM_001370404.1:c.4768C>G NP_001357333.1:p.Arg1590Gly missense NM_001370405.1:c.4771C>G NP_001357334.1:p.Arg1591Gly missense NM_001406663.1:c.4897C>G NP_001393592.1:p.Arg1633Gly missense NM_001406664.1:c.4828C>G NP_001393593.1:p.Arg1610Gly missense NM_001406665.1:c.4822C>G NP_001393594.1:p.Arg1608Gly missense NM_001406667.1:c.4792C>G NP_001393596.1:p.Arg1598Gly missense NM_001406668.1:c.4789C>G NP_001393597.1:p.Arg1597Gly missense NM_001406670.1:c.4720C>G NP_001393599.1:p.Arg1574Gly missense NM_001406671.1:c.4690C>G NP_001393600.1:p.Arg1564Gly missense NM_001406673.1:c.4687C>G NP_001393602.1:p.Arg1563Gly missense NM_001406675.1:c.4684C>G NP_001393604.1:p.Arg1562Gly missense NM_001406676.1:c.4681C>G NP_001393605.1:p.Arg1561Gly missense NM_001406677.1:c.4642C>G NP_001393606.1:p.Arg1548Gly missense NM_001406678.1:c.4588C>G NP_001393607.1:p.Arg1530Gly missense NM_001406679.1:c.4552C>G NP_001393608.1:p.Arg1518Gly missense NM_001406680.1:c.4300C>G NP_001393609.1:p.Arg1434Gly missense NM_001406681.1:c.4240C>G NP_001393610.1:p.Arg1414Gly missense NM_001406682.1:c.4231C>G NP_001393611.1:p.Arg1411Gly missense NM_001406683.1:c.4231C>G NP_001393612.1:p.Arg1411Gly missense NM_001406684.1:c.4228C>G NP_001393613.1:p.Arg1410Gly missense NM_001406685.1:c.4102C>G NP_001393614.1:p.Arg1368Gly missense NM_001406686.1:c.4102C>G NP_001393615.1:p.Arg1368Gly missense NM_001406687.1:c.4099C>G NP_001393616.1:p.Arg1367Gly missense NM_001406688.1:c.4099C>G NP_001393617.1:p.Arg1367Gly missense NM_001406689.1:c.3487C>G NP_001393618.1:p.Arg1163Gly missense NM_001406690.1:c.3427C>G NP_001393619.1:p.Arg1143Gly missense NM_001406691.1:c.3424C>G NP_001393620.1:p.Arg1142Gly missense NM_001406692.1:c.3358C>G NP_001393621.1:p.Arg1120Gly missense NM_001406693.1:c.3358C>G NP_001393622.1:p.Arg1120Gly missense NM_001406694.1:c.3358C>G NP_001393623.1:p.Arg1120Gly missense NM_001406695.1:c.3355C>G NP_001393624.1:p.Arg1119Gly missense NM_001406696.1:c.3355C>G NP_001393625.1:p.Arg1119Gly missense NM_001406697.1:c.3355C>G NP_001393626.1:p.Arg1119Gly missense NM_001406698.1:c.3097C>G NP_001393627.1:p.Arg1033Gly missense NM_021055.3:c.4771C>G NP_066399.2:p.Arg1591Gly missense NR_176225.1:n.4852C>G non-coding transcript variant NR_176226.1:n.5100C>G non-coding transcript variant NR_176227.1:n.5028C>G non-coding transcript variant NR_176228.1:n.4849C>G non-coding transcript variant NR_176229.1:n.4774C>G non-coding transcript variant NC_000016.10:g.2086782C>G NC_000016.9:g.2136783C>G NG_005895.1:g.42477C>G NG_008617.1:g.56439G>C LRG_487:g.42477C>G LRG_487t1:c.4900C>G LRG_487p1:p.Arg1634Gly - Protein change
- R1142G, R1367G, R1518G, R1519G, R1530G, R1531G, R1548G, R1563G, R1564G, R1574G, R1578G, R1591G, R1633G, R1119G, R1120G, R1390G, R1562G, R1597G, R1608G, R1610G, R1033G, R1143G, R1368G, R1410G, R1434G, R1561G, R1568G, R1598G, R1611G, R1163G, R1411G, R1414G, R1567G, R1590G, R1634G
- Other names
- -
- Canonical SPDI
- NC_000016.10:2086781:C:G
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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. |
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| TSC2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
10764 | 10963 | |
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
|
Jun 29, 2023 | RCV003851441.2 |
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. |
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|---|---|---|---|---|---|
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Uncertain significance
(Jun 29, 2023)
|
criteria provided, single submitter
Method: clinical testing
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Tuberous sclerosis 2
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004696749.1
First in ClinVar: Feb 28, 2024 Last updated: Feb 28, 2024 |
Comment:
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 … (more)
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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TSC2 protein function. This variant has not been reported in the literature in individuals affected with TSC2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1634 of the TSC2 protein (p.Arg1634Gly). (less)
|
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:
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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TSC2 protein function. This variant has not been reported in the literature in individuals affected with TSC2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1634 of the TSC2 protein (p.Arg1634Gly).
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 Sep 30, 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.