ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4621G>A (p.Asp1541Asn)

gnomAD frequency: 0.00001  dbSNP: rs796872464
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000644241 SCV000765932 likely benign Tuberous sclerosis 2 2025-01-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV001022800 SCV001184578 likely benign Hereditary cancer-predisposing syndrome 2023-05-09 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 RCV000644241 SCV002040212 likely benign Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV001022800 SCV002533959 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-17 criteria provided, single submitter curation
GeneDx RCV003225106 SCV003921748 uncertain significance not provided 2023-04-28 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 18466115)
Baylor Genetics RCV003465408 SCV004206812 uncertain significance Isolated focal cortical dysplasia type II 2023-10-05 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004004023 SCV004822178 uncertain significance Tuberous sclerosis syndrome 2023-08-15 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with asparagine at codon 1541 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 not been identified 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 RCV004533367 SCV004709765 uncertain significance TSC2-related disorder 2024-01-19 no assertion criteria provided clinical testing The TSC2 c.4621G>A variant is predicted to result in the amino acid substitution p.Asp1541Asn. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. 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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