Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001048478 | SCV001212487 | uncertain significance | Hypertrophic cardiomyopathy | 2020-12-15 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with clinical features of MYBPC3-related disease (Invitae). ClinVar contains an entry for this variant (Variation ID: 845417). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with histidine at codon 1070 of the MYBPC3 protein (p.Gln1070His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine. |
Color Diagnostics, |
RCV001183284 | SCV001348972 | uncertain significance | Cardiomyopathy | 2023-04-20 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamine with histidine at codon 1070 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 not been reported in individuals affected with MYBPC3-related disorders in the literature. This variant has not been identified 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. |
All of Us Research Program, |
RCV001048478 | SCV004836645 | uncertain significance | Hypertrophic cardiomyopathy | 2023-09-05 | criteria provided, single submitter | clinical testing | Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the fibronectin type 3 domain C9 of the MYBPC3 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant is rare in the general population and has been identified in 0/277264 chromosomes by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. |