ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3538A>G (p.Lys1180Glu)

gnomAD frequency: 0.00001  dbSNP: rs751708490
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000700174 SCV000828919 benign Tuberous sclerosis 2 2023-11-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV001020551 SCV001182045 likely benign Hereditary cancer-predisposing syndrome 2022-03-02 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.
Baylor Genetics RCV000700174 SCV001482867 uncertain significance Tuberous sclerosis 2 2020-05-21 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx RCV001592895 SCV001814173 uncertain significance not provided 2023-10-10 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Genome-Nilou Lab RCV000700174 SCV002039764 likely benign Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001592895 SCV004184506 uncertain significance not provided 2023-11-01 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003999702 SCV004820660 uncertain significance Tuberous sclerosis syndrome 2023-05-16 criteria provided, single submitter clinical testing This missense variant replaces lysine with glutamic acid at codon 1180 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 tuberous sclerosis complex in the literature. This variant has been identified in 1/250142 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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