Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000537623 | SCV000625953 | uncertain significance | Duchenne muscular dystrophy | 2024-07-24 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 2391 of the DMD protein (p.Lys2391Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DMD-related conditions. ClinVar contains an entry for this variant (Variation ID: 455930). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DMD protein function with a negative predictive value of 95%. 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. |
| Stanford Center for Inherited Cardiovascular Disease, |
RCV000786299 | SCV000925062 | uncertain significance | not provided | 2017-08-08 | no assertion criteria provided | provider interpretation | DMD p.Lys2391Arg ( c.7172A>G) Seen in a patient in our center with cardiomyopathy and a pathogenic MYH7 variant. The lab classifies this variant as a variant of uncertain significance. Given the lack of case data, the rarity, and the type of variation, we consider this variant a variant of uncertain significance and we do not feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). Of note, very few missense variants in this gene are pathogenic. Per the lab report, the variant has not been reported in association with disease. Per the lab report, in silico algorithms do not agree on potential impact on protein. The variant is not listed in the Genome Aggregation Consortium Dataset (gnomAD; http://gnomad.broadinstitute.org/), which currently includes variant calls on >140,000 unrelated individuals of African, Asian, European, Latino, and Ashkenazi descent. The average coverage at that site in gnomAD is .>20x. |