Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001363249 | SCV001559353 | uncertain significance | Hypertrophic cardiomyopathy | 2023-10-15 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with tyrosine, which is neutral and polar, at codon 1498 of the MYH7 protein (p.Phe1498Tyr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MYH7-related conditions. ClinVar contains an entry for this variant (Variation ID: 1054697). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
| Gene |
RCV001751716 | SCV002007224 | uncertain significance | not provided | 2020-02-24 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV002329367 | SCV002636761 | uncertain significance | Cardiovascular phenotype | 2021-12-07 | criteria provided, single submitter | clinical testing | The c.4493_4494delTCinsAT variant (also known as p.F1498Y), located in coding exon 30 of the MYH7 gene, results from an in-frame deletion of TC and insertion of AT at nucleotide positions 4493 to 4494. This results in the substitution of the phenylalanine residue for a tyrosine residue at codon 1498, an amino acid with highly similar properties. This alteration has been seen in an exome cohort, but detailed cardiovascular history was not provided (Homburger JR et al. Proc Natl Acad Sci U S A, 2016 06;113:6701-6). Based on data from gnomAD, this allele has an overall frequency of <0.01% (1/251492) total alleles studied. The highest observed frequency was <0.01% (1/16256) of African alleles. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Revvity Omics, |
RCV001751716 | SCV003817757 | uncertain significance | not provided | 2021-12-08 | criteria provided, single submitter | clinical testing | |
| Genetics and Molecular Pathology, |
RCV003447591 | SCV004175588 | uncertain significance | Hypertrophic cardiomyopathy 1 | 2021-10-12 | criteria provided, single submitter | clinical testing |