Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000468464 | SCV000552167 | uncertain significance | Desmin-related myofibrillar myopathy | 2022-03-26 | 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 227 of the DES protein (p.Arg227Cys). 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. ClinVar contains an entry for this variant (Variation ID: 411141). This missense change has been observed in individual(s) with dilated cardiomyopathy (DCM) (PMID: 28171858). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs767743962, gnomAD 0.003%). |
| 3billion | RCV001809412 | SCV002058134 | uncertain significance | Neurogenic scapuloperoneal syndrome, Kaeser type | 2022-01-03 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000008, PM2_M). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.734, PP3_P). A missense variant is a common mechanism associated with Scapuloperoneal syndrome (PP2_P). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. |