ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4888G>A (p.Val1630Met)

gnomAD frequency: 0.00001  dbSNP: rs886051796
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000371761 SCV000395663 uncertain significance Tuberous sclerosis syndrome 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV001079540 SCV000644578 benign Tuberous sclerosis 2 2024-01-25 criteria provided, single submitter clinical testing
GeneDx RCV000839227 SCV000981114 likely benign not provided 2020-02-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV001023201 SCV001185043 likely benign Hereditary cancer-predisposing syndrome 2023-01-17 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Genome-Nilou Lab RCV001079540 SCV002040229 likely benign Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001079540 SCV004360926 uncertain significance Tuberous sclerosis 2 2023-01-27 criteria provided, single submitter clinical testing This missense variant replaces valine with methionine at codon 1630 of the TSC2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TSC2-related disorders in the literature. This variant has been identified in 3/280892 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.
PreventionGenetics, part of Exact Sciences RCV004537797 SCV004724222 likely benign TSC2-related disorder 2024-01-10 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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