Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000696186 | SCV000824737 | uncertain significance | Hypertrophic cardiomyopathy | 2023-12-04 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1037 of the MYBPC3 protein (p.Arg1037Cys). 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 missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 25132132). ClinVar contains an entry for this variant (Variation ID: 574286). 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. |
| Color Diagnostics, |
RCV001190215 | SCV001357658 | uncertain significance | Cardiomyopathy | 2023-11-16 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with cysteine at codon 1037 of the MYBPC3 protein. Computational prediction tools indicate that this variant's impact on protein structure and function is inconclusive. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in two individuals affected with hypertrophic cardiomyopathy (PMID: 24865491, 25132132). One of these individuals also carried a second variant in the MuRF2 gene (PMID: 24865491). 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. |
| Fulgent Genetics, |
RCV002493205 | SCV002775066 | uncertain significance | Hypertrophic cardiomyopathy 4; Left ventricular noncompaction 10 | 2021-10-13 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003163201 | SCV003911371 | uncertain significance | Cardiovascular phenotype | 2022-12-30 | criteria provided, single submitter | clinical testing | The p.R1037C variant (also known as c.3109C>T), located in coding exon 29 of the MYBPC3 gene, results from a C to T substitution at nucleotide position 3109. The arginine at codon 1037 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported in a hypertrophic cardiomyopathy (HCM) cohort; however, clinical details were limited (Su M et al. Int J Mol Sci, 2014 May;15:9302-13; Wang J et al. Eur J Heart Fail, 2014 Sep;16:950-7). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |