Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000035652 | SCV000059303 | uncertain significance | not specified | 2014-06-18 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Pathogenic. The p.Ser212Arg variant in MYBPC3 has been reported in 1 individual with HCM (Olivotto 2008) an d was absent from large population studies. It has also been identified by our l aboratory in 2 Caucasian adults with HCM and segregated with the disease in 2 af fected relatives. Computational prediction tools and conservation analysis do no t provide strong support for or against an impact to the protein. The change to arginine (Arg) at position 212 was predicted to be benign using a computational tool clinically validated by our laboratory. This tool's benign prediction is es timated to be correct 89% of the time (Jordan 2011). However, this variant is pr edicted to create an alternative 5' splice site, and while this is not predictiv e enough to determine pathogenicity, it is consistent with the established mecha nism of disease for MYBPC3. In summary, though its clinical significance remains uncertain, its presence in multiple affected individuals, segregation with dise ase, and possible splicing impact raise suspicion that this variant may have a r ole in disease. |
| Eurofins Ntd Llc |
RCV000724638 | SCV000230882 | uncertain significance | not provided | 2015-03-13 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000797730 | SCV000937309 | pathogenic | Hypertrophic cardiomyopathy | 2024-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 212 of the MYBPC3 protein (p.Ser212Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with hypertrophic cardiomyopathy (PMID: 18533079, 27532257, 33782553; internal data). ClinVar contains an entry for this variant (Variation ID: 42776). 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. Studies have shown that this missense change alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 28679633). For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV000724638 | SCV002552598 | uncertain significance | not provided | 2022-07-25 | 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; In silico splicing algorithms predict this variant results in the creation of a cryptic splice donor site upstream of the natural splice donor site for intron 5; This variant is associated with the following publications: (PMID: 18533079, 27532257, 33782553, 28679633) |
| Ambry Genetics | RCV004018765 | SCV004938717 | uncertain significance | Cardiovascular phenotype | 2022-10-05 | criteria provided, single submitter | clinical testing | The c.636C>G (p.S212R) alteration is located in exon 5 (coding exon 5) of the MYBPC3 gene. This alteration results from a C to G substitution at nucleotide position 636, causing the serine (S) at amino acid position 212 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |