Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001174568 | SCV001337730 | uncertain significance | not specified | 2020-01-06 | criteria provided, single submitter | clinical testing | Variant summary: MYH6 c.71T>C (p.Leu24Pro) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251480 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.71T>C has been reported in the literature in one individual affected with Cardiomyopathy (Seidelmann_2017). The report does not provide unequivocal conclusions about association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Labcorp Genetics |
RCV001294383 | SCV001483258 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2023-03-27 | 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: 917551). This missense change has been observed in individual(s) with clinical features of MYH6-related conditions (PMID: 28087566). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 24 of the MYH6 protein (p.Leu24Pro). |
| Fulgent Genetics, |
RCV002505756 | SCV002817046 | uncertain significance | Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to | 2021-10-28 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003163385 | SCV003864565 | uncertain significance | Cardiovascular phenotype | 2023-01-18 | criteria provided, single submitter | clinical testing | The p.L24P variant (also known as c.71T>C), located in coding exon 1 of the MYH6 gene, results from a T to C substitution at nucleotide position 71. The leucine at codon 24 is replaced by proline, an amino acid with similar properties. This alteration has been reported in a subject with dilated cardiomyopathy (DCM), atrial fibrillation and bradycardia who also carried a second missense alteration in MYH6 (Seidelmann SB et al. Circ Cardiovasc Genet, 2017 Feb;10:). This amino acid position is well 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. |