Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000820641 | SCV000961361 | uncertain significance | Hypertrophic cardiomyopathy | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 721 of the MYBPC3 protein (p.Thr721Ile). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 662896). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
Petrovsky National Research Centre of Surgery, |
RCV001267643 | SCV001443818 | uncertain significance | See cases | 2020-11-18 | criteria provided, single submitter | clinical testing | We observed a genetic variant c.2162C>T (p.T721I) in MYBPC3 gene in a male 5 month proband diagnosed with left ventricular non-compaction and dilatation of cardiac chambers. The p.T721I genetic variant is present in gnomAD database with frequency of 4.076e-6, thus being rare. Online in silico tools predict the p.T721I genetic variant to be probably pathogenic. However, in the absence of functional studies and/or segregation analysis we could only classify the p.T721I genetic variant as a variant of uncertain clinical significance. |
Gene |
RCV002462185 | SCV002757379 | uncertain significance | not provided | 2022-05-23 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |