ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2167A>G (p.Ile723Val)

dbSNP: rs764725850
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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 RCV001084101 SCV000285281 benign Tuberous sclerosis 2 2024-01-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV000564827 SCV000675650 likely benign Hereditary cancer-predisposing syndrome 2023-07-06 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.
Eurofins Ntd Llc (ga) RCV000596298 SCV000701637 uncertain significance not provided 2016-10-04 criteria provided, single submitter clinical testing
GeneDx RCV000596298 SCV001812618 likely benign not provided 2019-07-24 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001084101 SCV002039626 likely benign Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Johns Hopkins Genomics, Johns Hopkins University RCV001084101 SCV003839115 uncertain significance Tuberous sclerosis 2 2022-12-12 criteria provided, single submitter clinical testing This TSC2 missense variant (rs764725850) is rare (<0.1%) in a large population dataset (gnomAD v2.1.1: 3/251236 total alleles; 0.0012%; no homozygotes). It has been reported in ClinVar (Variation ID 237983), but not in the literature, to our knowledge. Two bioinformatic tools queried predict that this substitution would be tolerated. While the isoleucine residue at this position is evolutionarily conserved across many of the species assessed, several species have a different amino acid at this position, including 4 species with valine. We consider the clinical significance of c.2167A>G; p.Ile723Val in TSC2 to be uncertain at this time.
CeGaT Center for Human Genetics Tuebingen RCV000596298 SCV004133831 likely benign not provided 2023-10-01 criteria provided, single submitter clinical testing TSC2: BP4, BS2
All of Us Research Program, National Institutes of Health RCV003998811 SCV004824342 uncertain significance Tuberous sclerosis syndrome 2024-02-05 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 723 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 hereditary cancer in the literature. This variant has been identified in 3/251236 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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