Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000156245 | SCV000205961 | uncertain significance | not specified | 2013-12-11 | criteria provided, single submitter | clinical testing | The Glu838Gln variant in MYBPC3 has not been previously reported in individuals with cardiomyopathy or large European American and African American cohorts. Co mputational analyses (biochemical amino acid properties, conservation, AlignGVGD , PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Additional information is needed to fully assess the clinical sig nificance of the Glu838Gln variant. |
Invitae | RCV001351680 | SCV001546173 | uncertain significance | Hypertrophic cardiomyopathy | 2023-12-21 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 838 of the MYBPC3 protein (p.Glu838Gln). This variant is present in population databases (rs397515969, gnomAD 0.004%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 32826072). ClinVar contains an entry for this variant (Variation ID: 179456). 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. |
Fulgent Genetics, |
RCV002484948 | SCV002779047 | uncertain significance | Hypertrophic cardiomyopathy 4; Left ventricular noncompaction 10 | 2021-09-14 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003162637 | SCV003911377 | uncertain significance | Cardiovascular phenotype | 2023-02-08 | criteria provided, single submitter | clinical testing | The p.E838Q variant (also known as c.2512G>C), located in coding exon 25 of the MYBPC3 gene, results from a G to C substitution at nucleotide position 2512. The glutamic acid at codon 838 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been reported in a dilated cardiomyopathy (DCM) cohort (Peña-Peña ML et al. Med Clin (Barc), 2021 May;156:485-495). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |