ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2257G>A (p.Ala753Thr)

gnomAD frequency: 0.00001  dbSNP: rs574205203
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130092 SCV000184921 likely benign Hereditary cancer-predisposing syndrome 2015-10-28 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000530366 SCV000644333 benign Tuberous sclerosis 2 2023-12-06 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000530366 SCV002041450 benign Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000530366 SCV003928050 uncertain significance Tuberous sclerosis 2 2023-03-16 criteria provided, single submitter clinical testing The TSC2 c.2257G>A (p.Ala753Thr) missense change has a maximum subpopulation frequency of 0.005% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in individuals with tuberous sclerosis complex. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
PreventionGenetics, part of Exact Sciences RCV004528853 SCV004108770 uncertain significance TSC2-related disorder 2023-07-20 criteria provided, single submitter clinical testing The TSC2 c.2257G>A variant is predicted to result in the amino acid substitution p.Ala753Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0050% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-2122886-G-A). It has conflicting interpretations ranging from benign to uncertain in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/141526/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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