Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000158226 | SCV000208161 | uncertain significance | not provided | 2014-05-28 | criteria provided, single submitter | clinical testing | This variant is denoted p.Gln1103Pro (CAG>CCG): c.3308 A>C in exon 30 of the MYBPC3 gene (NM_000256.3). A variant of unknown significance has been identified in the MYBPC3 gene. The Q1103P variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The Q1103P variant was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is conserved across species. In addition, the Q1103P variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, missense mutations in nearby residues (E1096K, T1109I, E1111G, F1113I) have been reported in association with HCM, supporting the functional importance of this region of the protein. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in HCM panel(s). |
| Invitae | RCV001850210 | SCV002248544 | uncertain significance | Hypertrophic cardiomyopathy | 2021-07-07 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with proline at codon 1103 of the MYBPC3 protein (p.Gln1103Pro). The glutamine residue is highly conserved and there is a moderate physicochemical difference between glutamine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 181006). 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. 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. |