ClinVar Genomic variation as it relates to human health
NM_000548.5(TSC2):c.3185T>C (p.Val1062Ala)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000548.5(TSC2):c.3185T>C (p.Val1062Ala)
Variation ID: 1713547 Accession: VCV001713547.5
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 16p13.3 16: 2079329 (GRCh38) [ NCBI UCSC ] 16: 2129330 (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 5, 2022 May 1, 2024 Nov 6, 2023 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000548.5:c.3185T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000539.2:p.Val1062Ala missense NM_001077183.3:c.3053T>C NP_001070651.1:p.Val1018Ala missense NM_001114382.3:c.3185T>C NP_001107854.1:p.Val1062Ala missense NM_001318827.2:c.2945T>C NP_001305756.1:p.Val982Ala missense NM_001318829.2:c.2909T>C NP_001305758.1:p.Val970Ala missense NM_001318831.2:c.2453T>C NP_001305760.1:p.Val818Ala missense NM_001318832.2:c.3086T>C NP_001305761.1:p.Val1029Ala missense NM_001363528.2:c.3056T>C NP_001350457.1:p.Val1019Ala missense NM_001370404.1:c.3053T>C NP_001357333.1:p.Val1018Ala missense NM_001370405.1:c.3056T>C NP_001357334.1:p.Val1019Ala missense NM_001406663.1:c.3182T>C NP_001393592.1:p.Val1061Ala missense NM_001406664.1:c.3182T>C NP_001393593.1:p.Val1061Ala missense NM_001406665.1:c.3053T>C NP_001393594.1:p.Val1018Ala missense NM_001406667.1:c.3146T>C NP_001393596.1:p.Val1049Ala missense NM_001406668.1:c.3143T>C NP_001393597.1:p.Val1048Ala missense NM_001406670.1:c.3074T>C NP_001393599.1:p.Val1025Ala missense NM_001406671.1:c.3044T>C NP_001393600.1:p.Val1015Ala missense NM_001406673.1:c.3041T>C NP_001393602.1:p.Val1014Ala missense NM_001406675.1:c.3038T>C NP_001393604.1:p.Val1013Ala missense NM_001406676.1:c.3035T>C NP_001393605.1:p.Val1012Ala missense NM_001406677.1:c.2996T>C NP_001393606.1:p.Val999Ala missense NM_001406678.1:c.2942T>C NP_001393607.1:p.Val981Ala missense NM_001406679.1:c.2906T>C NP_001393608.1:p.Val969Ala missense NM_001406680.1:c.2585T>C NP_001393609.1:p.Val862Ala missense NM_001406681.1:c.2594T>C NP_001393610.1:p.Val865Ala missense NM_001406682.1:c.2585T>C NP_001393611.1:p.Val862Ala missense NM_001406683.1:c.2585T>C NP_001393612.1:p.Val862Ala missense NM_001406684.1:c.2582T>C NP_001393613.1:p.Val861Ala missense NM_001406685.1:c.2456T>C NP_001393614.1:p.Val819Ala missense NM_001406686.1:c.2456T>C NP_001393615.1:p.Val819Ala missense NM_001406687.1:c.2453T>C NP_001393616.1:p.Val818Ala missense NM_001406688.1:c.2453T>C NP_001393617.1:p.Val818Ala missense NM_001406689.1:c.1841T>C NP_001393618.1:p.Val614Ala missense NM_001406690.1:c.1712T>C NP_001393619.1:p.Val571Ala missense NM_001406691.1:c.1709T>C NP_001393620.1:p.Val570Ala missense NM_001406692.1:c.1712T>C NP_001393621.1:p.Val571Ala missense NM_001406693.1:c.1712T>C NP_001393622.1:p.Val571Ala missense NM_001406694.1:c.1712T>C NP_001393623.1:p.Val571Ala missense NM_001406695.1:c.1709T>C NP_001393624.1:p.Val570Ala missense NM_001406696.1:c.1709T>C NP_001393625.1:p.Val570Ala missense NM_001406697.1:c.1709T>C NP_001393626.1:p.Val570Ala missense NM_001406698.1:c.1451T>C NP_001393627.1:p.Val484Ala missense NM_021055.3:c.3056T>C NP_066399.2:p.Val1019Ala missense NR_176225.1:n.3206T>C NR_176226.1:n.3385T>C NR_176227.1:n.3382T>C NR_176228.1:n.3203T>C NR_176229.1:n.3163T>C NC_000016.10:g.2079329T>C NC_000016.9:g.2129330T>C NG_005895.1:g.35024T>C LRG_487:g.35024T>C LRG_487t1:c.3185T>C LRG_487p1:p.Val1062Ala - Protein change
- V1012A, V1013A, V1014A, V1015A, V1018A, V1019A, V1025A, V1029A, V1048A, V1049A, V1061A, V1062A, V484A, V570A, V571A, V614A, V818A, V819A, V861A, V862A, V865A, V969A, V970A, V981A, V982A, V999A
- Other names
- -
- Canonical SPDI
- NC_000016.10:2079328:T:C
-
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 |
10739 | 10936 |
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
|
Oct 28, 2022 | RCV002295550.4 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Nov 6, 2023 | RCV004047645.1 |
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. |
|
---|---|---|---|---|---|
Uncertain significance
(Oct 28, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Tuberous sclerosis 2
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002596947.3
First in ClinVar: Nov 05, 2022 Last updated: Feb 20, 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 valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1062 of the TSC2 protein (p.Val1062Ala). (less)
|
|
Uncertain significance
(Nov 06, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV005036399.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
The p.V1062A variant (also known as c.3185T>C), located in coding exon 27 of the TSC2 gene, results from a T to C substitution at nucleotide … (more)
The p.V1062A variant (also known as c.3185T>C), located in coding exon 27 of the TSC2 gene, results from a T to C substitution at nucleotide position 3185. The valine at codon 1062 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
|
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. |
Citations for germline classification of this variant
HelpThere 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 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.