Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000151219 | SCV000199071 | uncertain significance | not specified | 2014-07-15 | criteria provided, single submitter | clinical testing | The Leu994Met variant in MYH6 has not been previously reported in individuals wi th cardiomyopathy or in large population studies. Computational prediction tools and conservation analysis do not provide strong support for or against an impac t to the protein. In summary, the clinical significance of the Leu994Met variant is uncertain. |
| Labcorp Genetics |
RCV000706239 | SCV000835278 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2024-12-15 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 994 of the MYH6 protein (p.Leu994Met). This variant is present in population databases (rs727503238, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with MYH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 164237). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt MYH6 protein function with a negative predictive value of 80%. 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. |
| Fulgent Genetics, |
RCV002498698 | SCV002806990 | uncertain significance | Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to | 2022-02-10 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003352778 | SCV004078052 | uncertain significance | Cardiovascular phenotype | 2023-07-29 | criteria provided, single submitter | clinical testing | The p.L994M variant (also known as c.2980C>A), located in coding exon 21 of the MYH6 gene, results from a C to A substitution at nucleotide position 2980. The leucine at codon 994 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |
| Prevention |
RCV004528876 | SCV004105249 | uncertain significance | MYH6-related disorder | 2022-09-12 | criteria provided, single submitter | clinical testing | The MYH6 c.2980C>A variant is predicted to result in the amino acid substitution p.Leu994Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0026% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/14-23862676-G-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |