Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000158642 | SCV000208577 | uncertain significance | not provided | 2019-04-10 | criteria provided, single submitter | clinical testing | Not observed [at a significant frequency] 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: 29121657) |
Invitae | RCV000628978 | SCV000749888 | uncertain significance | Hypertrophic cardiomyopathy | 2021-09-02 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with glycine at codon 1400 of the MYH7 protein (p.Ala1400Gly). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and glycine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 29121657). ClinVar contains an entry for this variant (Variation ID: 181248). 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"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Ambry Genetics | RCV002326901 | SCV002628592 | uncertain significance | Cardiovascular phenotype | 2020-03-19 | criteria provided, single submitter | clinical testing | The p.A1400G variant (also known as c.4199C>G), located in coding exon 29 of the MYH7 gene, results from a C to G substitution at nucleotide position 4199. The alanine at codon 1400 is replaced by glycine, an amino acid with similar properties. This variant has been detected in a hypertrophic cardiomyopathy cohort; however, details were limited (Viswanathan SK et al. PLoS ONE, 2017 Nov;12:e0187948). 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. |