ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.226C>T (p.His76Tyr) (rs574779350)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000190081 SCV000243756 uncertain significance not specified 2014-11-21 criteria provided, single submitter clinical testing p.His76Tyr (CAC>TAC): c.226 C>T in exon 4 of the TSC2 gene (NM_000548.3) A variant of unknown significance has been identified in the TSC2 gene. The H76Y variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The H76Y 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 in mammals, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense mutations in a nearby residue (E75K, E75G) have been reported in association with tuberous sclerosis . Based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.The variant is found in EPILEPSY panel(s).
Illumina Clinical Services Laboratory,Illumina RCV000367424 SCV000395551 likely benign Tuberous sclerosis syndrome 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000470663 SCV000544588 benign not provided 2019-02-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV000565361 SCV000675571 uncertain significance Hereditary cancer-predisposing syndrome 2018-01-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence

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