Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000497997 | SCV000589458 | uncertain significance | not provided | 2018-11-08 | criteria provided, single submitter | clinical testing | Although the D1106N variant has not been published as a pathogenic variant or as a benign variant to our knowledge, it has previously been identified in one other unrelated individual who had DNA-based testing for cardiomyopathy at GeneDx. This variant was not observed in approximately 6,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The D1106N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, missense variants in nearby residues (T1109I, E1111G, F1113I, V1115I) have been reported in the Human Gene Mutation Database in association with HCM (Stenson et al., 2014), 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 variant or a rare benign variant. |
| Invitae | RCV001235231 | SCV001407908 | uncertain significance | Hypertrophic cardiomyopathy | 2023-06-17 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 431894). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 27532257, 32492895, 33658040). 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 sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1106 of the MYBPC3 protein (p.Asp1106Asn). |