Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Biesecker Lab/Clinical Genomics Section, |
RCV000172017 | SCV000050984 | uncertain significance | not provided | 2013-06-24 | criteria provided, single submitter | research | |
Gene |
RCV000172017 | SCV000208132 | uncertain significance | not provided | 2022-08-02 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Invitae | RCV001063574 | SCV001228427 | uncertain significance | Hypertrophic cardiomyopathy | 2023-07-25 | 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. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 180988). This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. 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 sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 51 of the MYBPC3 protein (p.Ala51Ser). |
Color Diagnostics, |
RCV001179378 | SCV001344032 | uncertain significance | Cardiomyopathy | 2023-01-19 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with serine at codon 51 of the MYBPC3 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has reported in an individual from a cohort of participants undergoing whole exome sequencing that were not pre-selected for a personal or family history of arrhythmia, cardiomyopathy or sudden cardiac death (PMID: 23861362); it has not been reported in individuals affected with MYBPC3-related disorders in the literature. This variant has been identified in 4/239086 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |