Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000621002 | SCV000739954 | uncertain significance | Cardiovascular phenotype | 2016-05-25 | criteria provided, single submitter | clinical testing | The p.L873P variant (also known as c.2618T>C), located in coding exon 20 of the MYH7 gene, results from a T to C substitution at nucleotide position 2618. The leucine at codon 873 is replaced by proline, an amino acid with some similar properties. In a hypertrophic cardiomyopathy (HCM) cohort, this variant was reported in one patient (Marsiglia JD et al. Am Heart J. 2013;166(4):775-82). This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001384952 | SCV001584655 | pathogenic | Hypertrophic cardiomyopathy | 2020-04-30 | criteria provided, single submitter | clinical testing | This variant has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 24093860, Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 520274). For these reasons, this variant has been classified as Pathogenic. This variant is found within a region of MYH7 between codons 181 and 937 that contains the majority of the myosin head domain. Missense variants in this region have been shown to be significantly overrepresented in individuals with hypertrophic cardiomyopathy (PMID: 27532257). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 873 of the MYH7 protein (p.Leu873Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. |