Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000482289 | SCV000573042 | uncertain significance | not provided | 2018-02-26 | criteria provided, single submitter | clinical testing | The S1465L variant has not been published as pathogenic or been reported as benign to our knowledge. The S1465L variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Though this substitution occurs at a position where amino acids with similar properties to serine are tolerated across species, S1465L is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Nevertheless, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. |
| Fulgent Genetics, |
RCV002489173 | SCV002778738 | uncertain significance | Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to | 2021-10-17 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV005090973 | SCV005754849 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2025-01-29 | 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 1465 of the MYH6 protein (p.Ser1465Leu). This variant is present in population databases (rs766327056, gnomAD 0.0009%). 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: 423354). 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 expected to disrupt MYH6 protein function with a positive 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. |