Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001721014 | SCV000209293 | likely benign | not provided | 2020-10-22 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 30297972) |
Stanford Center for Inherited Cardiovascular Disease, |
RCV000159347 | SCV000280538 | uncertain significance | not specified | 2014-04-15 | no assertion criteria provided | clinical testing | Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. p.Lys66Asn (c.198G>C) in TPM1: This variant is novel. It has not been observed in any cases of HCM or control individuals to date. In silico analysis with PolyPhen-2 predicts the variant to be probably damaging; and Mutation Taster predicts the variant to be disease-causing. Per GeneDx’s in silico analysis, they predict this variant to be benign to the protein structure/function. Lys66Asn results in a semi-conservative amino acid substitution of a positively charged Lysine with a neutral, polar Asparagine at a position that is not completely conserved across species. No other disease-causing variants have been reported at this codon. There is a nearby missense variant, p.E54K, which has been weakly associated with DCM in one individual. This variant is also referred to as p.K5N, in the literature. In total the variant has not been seen in 6,500 published controls and individuals from publically available population datasets. There is no variation at codon 66 listed in the NHLBI Exome Sequencing Project dataset, which currently includes variant calls on ~6500 Caucasian and African American individuals (as of 6/19/13). There is also no variation at this codon listed in dbSNP or 1000 genomes (as of 6/19/13). |