Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000466153 | SCV000546256 | likely pathogenic | Hypertrophic cardiomyopathy | 2018-01-22 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. A different missense substitution at this codon (p.Ile730Asn) has been determined to be likely pathogenic (PMID: 25935763). This suggests that the isoleucine residue is critical for MYH7 protein function and that other missense substitutions at this position may also be deleterious. A computational algorithm designed to assess the pathogenicity of variants in MYH7 with regard to hypertrophic cardiomyopathy predicted this sequence change to be deleterious. The algorithm has a sensitivity of 94% and a specificity of 89% (PMID: 21310275). 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). This variant has been reported in two individuals affected with hypertrophic cardiomyopathy (PMID: 22429680, Invitae). ClinVar contains an entry for this variant (Variation ID: 407193). This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with threonine at codon 730 of the MYH7 protein (p.Ile730Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. |
| Gene |
RCV001564801 | SCV001788019 | likely pathogenic | not provided | 2020-01-17 | criteria provided, single submitter | clinical testing | Reported in ClinVar as likely pathogenic (ClinVar Variant ID# 407193; Landrum et al., 2016); Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 22429680) |