Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000243044 | SCV000318096 | uncertain significance | Cardiovascular phenotype | 2012-12-13 | criteria provided, single submitter | clinical testing | There is insufficient or conflicting evidence for classification of this alteration. |
Invitae | RCV000808501 | SCV000948611 | uncertain significance | Hypertrophic cardiomyopathy | 2021-06-30 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 263460). This sequence change replaces leucine with histidine at codon 889 of the MYH7 protein (p.Leu889His). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 20031618; Invitae). 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. 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). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |