ClinVar Miner

Submissions for variant NM_000368.5(TSC1):c.1012A>G (p.Ile338Val)

dbSNP: rs2131974315
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001973137 SCV002256585 uncertain significance Tuberous sclerosis 1 2023-04-15 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with TSC1-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TSC1 protein function. ClinVar contains an entry for this variant (Variation ID: 1469949). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 338 of the TSC1 protein (p.Ile338Val).
All of Us Research Program, National Institutes of Health RCV004011014 SCV004825246 uncertain significance Tuberous sclerosis syndrome 2023-08-15 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 338 of the TSC1 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 TSC1-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.

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