Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Hudson |
RCV000656550 | SCV000778582 | uncertain significance | Hypertrophic cardiomyopathy 1 | 2018-03-12 | criteria provided, single submitter | research | |
Ambry Genetics | RCV002442387 | SCV002732398 | uncertain significance | Cardiovascular phenotype | 2018-12-24 | criteria provided, single submitter | clinical testing | The p.L781M variant (also known as c.2341C>A), located in coding exon 19 of the MYH7 gene, results from a C to A substitution at nucleotide position 2341. The leucine at codon 781 is replaced by methionine, an amino acid with highly similar properties. This alteration has been detected once in a cohort of individuals with hypertrophic cardiomyopathy (HCM) (Wang J et al. Eur. J. Heart Fail., 2014 Sep;16:950-7). In addition, authors performed structural analysis on this alteration and determined that it impairs MYH7 lever arm compliance (Robert-Paganin J et al. Nat Commun, 2018 10;9:4019). A different alteration located at the same position, p.L781P, has also been detected in individuals with hypertrophic cardiomyopathy (Alfares AA et al. Genet. Med., 2015 Nov;17:880-8; Walsh R et al. Genet. Med., 2017 02;19:192-203). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |