Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000037501 | SCV000061159 | uncertain significance | not specified | 2011-12-23 | criteria provided, single submitter | clinical testing | The Val1434Ile variant (MYH6) has not been previously reported nor previously id entified by our laboratory. Valine (Val) at position 1434 is moderately conserve d in evolutionarily distant species (frog carries a leucine), and this informati on is insufficient to predict if a change would impact the protein. Computationa l predictions on the impact to the protein are mixed (PolyPhen2 = benign, SIFT = pathogenic), though the accuracy of these tools is unknown. Additional informat ion is needed to fully assess the clinical significance of the Val1434Ile varian t. |
Invitae | RCV001852776 | SCV002266667 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2021-10-05 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 44508). This variant has not been reported in the literature in individuals affected with MYH6-related conditions. This variant is present in population databases (rs397516769, ExAC 0.01%). This sequence change replaces valine with isoleucine at codon 1434 of the MYH6 protein (p.Val1434Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. |
Fulgent Genetics, |
RCV002482988 | SCV002788813 | uncertain significance | Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to | 2021-08-20 | criteria provided, single submitter | clinical testing |