ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.2026T>A (p.Trp676Arg) (rs748901883)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189817 SCV000243469 uncertain significance not provided 2018-05-21 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the TSC1 gene. The W676R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The W676R variant is observed in 2/66348 (0.003%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). TheW676R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, the vast majority of TSC1 pathogenic variants result in protein truncation, while missense variants have been reported only rarely (Northrup et al., 2011; Au et al., 2007). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000189817 SCV000552380 likely benign not provided 2019-02-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV001014108 SCV001174782 uncertain significance Hereditary cancer-predisposing syndrome 2018-01-19 criteria provided, single submitter clinical testing Insufficient or conflicting evidence

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