Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000534813 | SCV000648275 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2024-03-10 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1838 of the MYH6 protein (p.Ser1838Leu). This variant is present in population databases (rs747673552, gnomAD 0.02%). 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: 470547). 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 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000587278 | SCV000697928 | uncertain significance | not provided | 2017-03-13 | criteria provided, single submitter | clinical testing | Variant summary: The MYH6 c.5513C>T (p.Ser1838Leu) variant involves the alteration of a conserved nucleotide. 2/3 in silico tools predict a damaging outcome for this variant (SNPs&GO and MutationTaster not captured due to low reliability index). This variant was found in 5/121300 control chromosomes at a frequency of 0.0000412, which is approximately 2 times the estimated maximal expected allele frequency of a pathogenic MYH6 variant (0.000025), suggesting this variant is likely a benign polymorphism. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as VUS-possibly benign. |
| Ambry Genetics | RCV002350321 | SCV002648681 | uncertain significance | Cardiovascular phenotype | 2023-10-15 | criteria provided, single submitter | clinical testing | The p.S1838L variant (also known as c.5513C>T), located in coding exon 34 of the MYH6 gene, results from a C to T substitution at nucleotide position 5513. The serine at codon 1838 is replaced by leucine, an amino acid with dissimilar properties. 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. |
| Fulgent Genetics, |
RCV002483465 | SCV002788424 | uncertain significance | Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to | 2021-10-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000587278 | SCV005888868 | uncertain significance | not provided | 2024-09-13 | criteria provided, single submitter | clinical testing | In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |