Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000035613 | SCV000059264 | uncertain significance | not specified | 2015-08-13 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The p.Ala125Ser var iant in MYBPC3 has been identified by our laboratory in one individual with HCM and was present in 1/8418 European chromosomes screened by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs370958401). Alanine (A la) at position 125 is not conserved in evolution and the change to serine (Ser) was predicted to be benign using a computational tool clinically validated by o ur laboratory. This tool's benign prediction is estimated to be correct 89% of t he time (Jordan 2011). In summary, while the clinical significance of the p.Ala1 25Ser variant is uncertain, these data suggest that it is more likely to be beni gn. |
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV000627140 | SCV000747957 | uncertain significance | Primary familial hypertrophic cardiomyopathy | 2017-06-26 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000629003 | SCV000749913 | uncertain significance | Hypertrophic cardiomyopathy | 2023-08-14 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 42738). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 27532257). This variant is present in population databases (rs370958401, gnomAD 0.007%). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 125 of the MYBPC3 protein (p.Ala125Ser). 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. |
Gene |
RCV001547624 | SCV001767376 | uncertain significance | not provided | 2021-03-04 | criteria provided, single submitter | clinical testing | Reported in patients referred for hypertrophic cardiomyopathy (Walsh et al., 2017); Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 42738; Landrum et al., 2016); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27532257) |
CHEO Genetics Diagnostic Laboratory, |
RCV003486551 | SCV004239386 | uncertain significance | Cardiomyopathy | 2022-10-05 | criteria provided, single submitter | clinical testing |