ClinVar Miner

Submissions for variant NM_004006.2(DMD):c.7172A>G (p.Lys2391Arg) (rs1556930538)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000537623 SCV000625953 uncertain significance Duchenne muscular dystrophy 2017-03-26 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 2391 of the DMD protein (p.Lys2391Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a DMD-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Stanford Center for Inherited Cardiovascular Disease, Stanford University 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.

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