ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.1015G>A (p.Val339Ile)

gnomAD frequency: 0.00002  dbSNP: rs559727962
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000644222 SCV000765913 likely benign Tuberous sclerosis 2 2024-11-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV001017006 SCV001178026 benign Hereditary cancer-predisposing syndrome 2022-09-28 criteria provided, single submitter clinical testing This alteration is classified as 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 RCV000644222 SCV002041121 likely benign Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004533366 SCV004113566 uncertain significance TSC2-related disorder 2023-02-28 criteria provided, single submitter clinical testing The TSC2 c.1015G>A variant is predicted to result in the amino acid substitution p.Val339Ile. To our knowledge, this variant has not been reported in the literature in association with TSC2-related disease. This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-2110710-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
All of Us Research Program, National Institutes of Health RCV004004017 SCV004817061 uncertain significance Tuberous sclerosis syndrome 2024-05-14 criteria provided, single submitter clinical testing This missense variant replaces valine with isoleucine at codon 339 of the TSC2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with tuberous sclerosis complex in the literature. This variant has been identified in 5/251362 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.

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