Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Heart Center, |
RCV000850017 | SCV000992159 | likely pathogenic | Left ventricular noncompaction 10 | 2018-12-01 | criteria provided, single submitter | research | |
Color Diagnostics, |
RCV001525436 | SCV001735535 | uncertain significance | Cardiomyopathy | 2020-08-06 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with arginine at codon 811 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 been reported in several individuals affected with hypertrophic cardiomyopathy (PMID: 12707239, 31534214; cardiodb.org; van Velzen 2018, dissertation, Erasmus University Rotterdam). 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. |
Invitae | RCV001858463 | SCV002294385 | uncertain significance | Hypertrophic cardiomyopathy | 2023-01-30 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 689323). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 12707239, 27532257, 33782553). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 811 of the MYBPC3 protein (p.Lys811Arg). |