Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Centre for Mendelian Genomics, |
RCV001196060 | SCV001366489 | uncertain significance | Hypertrophic cardiomyopathy 26 | 2019-03-21 | criteria provided, single submitter | clinical testing | This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PP3. |
| Invitae | RCV001863100 | SCV002302860 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2020-12-02 | 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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with FLNC-related conditions. ClinVar contains an entry for this variant (Variation ID: 930416). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces arginine with tryptophan at codon 2641 of the FLNC protein (p.Arg2641Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. |