Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000151223 | SCV000199083 | uncertain significance | not specified | 2013-06-14 | criteria provided, single submitter | clinical testing | The Ala227Thr variant in MYH6 has not been reported in individuals with cardiomy opathy, but has been identified in 1.8% (2/110) of Puerto Rican chromosomes by t he 1000 Genomes Project (dbSNP rs201828188). Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not pro vide strong support for or against an impact to the protein. The presence of thi s variant in the general population raises the possibility that it may be benign but this additional information is needed to establish this with confidence |
| Ambry Genetics | RCV000253650 | SCV000318353 | uncertain significance | Cardiovascular phenotype | 2022-05-31 | criteria provided, single submitter | clinical testing | The p.A227T variant (also known as c.679G>A), located in coding exon 6 of the MYH6 gene, results from a G to A substitution at nucleotide position 679. The alanine at codon 227 is replaced by threonine, an amino acid with similar properties. This variant was reported in one individual from a pediatric dilated cardiomyopathy (DCM) cohort; however, clinical details were limited (Burstein DS et al. Pediatr Res, 2021 05;89:1470-1476). This variant was also described in a child with progeroid features with no known cardiac findings, who had additional co-occurring de novo variants also detected on exome analysis (Hernandez-Hernandez C et al. AME Case Rep, 2021 Oct;5:40). This amino acid position is 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. |
| Invitae | RCV000793999 | SCV000933381 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2022-12-06 | criteria provided, single submitter | clinical testing | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MYH6 protein function. ClinVar contains an entry for this variant (Variation ID: 164254). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 32746448). This variant is present in population databases (rs201828188, gnomAD 0.01%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 227 of the MYH6 protein (p.Ala227Thr). |