Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000619793 | SCV000739962 | uncertain significance | Cardiovascular phenotype | 2019-09-20 | criteria provided, single submitter | clinical testing | The p.G354S variant (also known as c.1060G>A), located in coding exon 10 of the MYH7 gene, results from a G to A substitution at nucleotide position 1060. The glycine at codon 354 is replaced by serine, an amino acid with similar properties. This variant has been detected in an individual from a hypertrophic cardiomyopathy cohort; however, clinical details were limited (Alfares AA et al. Genet. Med., 2015 Nov;17:880-8). 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 | RCV000800797 | SCV000940532 | uncertain significance | Hypertrophic cardiomyopathy | 2022-06-26 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 354 of the MYH7 protein (p.Gly354Ser). This variant is present in population databases (rs727503270, gnomAD 0.002%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy or referred for genetic testing (PMID: 25611685, 27532257). ClinVar contains an entry for this variant (Variation ID: 164380). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |
| Ai |
RCV002223791 | SCV002503016 | uncertain significance | not provided | 2021-11-21 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002505153 | SCV002814575 | uncertain significance | Hypertrophic cardiomyopathy 1; Myopathy, myosin storage, autosomal recessive; Myosin storage myopathy; Congenital myopathy with fiber type disproportion; Dilated cardiomyopathy 1S; MYH7-related skeletal myopathy | 2021-08-20 | criteria provided, single submitter | clinical testing | |
| Laboratory for Molecular Medicine, |
RCV000151299 | SCV000199243 | uncertain significance | not specified | 2014-03-07 | no assertion criteria provided | clinical testing | proposed classification - variant undergoing re-assessment, contact laboratory |