ClinVar

Description

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.Glu1468Lys (c.4402G>A) in the MYH7 gene. The variant is novel. This is a non-conservative amino acid change with an acidic polar glutamic acid replaced with a basic polar lysine. The glutamic acid at position 1468 is completely conserved across species. In silico analysis with PolyPhen predicts the variant to be probably damaging with a score of 0.990. Mutation Taster predicts this variant to be disease causing with a score of 56. No other disease-causing variants have been reported at this or nearby codons (+/- 5 codons). The variant was not observed in 200 presumed healthy individuals of Caucasian and African-American ancestry at GeneDx. There is no variation at codon 1468 listed in the NHLBI Exome Sequencing Project dataset, which currently includes variant calls on ~6,500 Caucasian and African American individuals (as of 6/20/13. There is also no variant at codon 1468 in 1000 genomes or dbSNP (as of 6/20/13). There is currently insufficient data available on the variant to determine if it causes cardiomyopathy, however the data that is available does suggest it may be pathogenic. Segregation analysis could help clarify the status of this variant.