ClinVar Miner

Submissions for variant NM_004006.2(DMD):c.3971G>A (p.Arg1324His) (rs768990357)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000536434 SCV000625896 uncertain significance Duchenne muscular dystrophy 2017-04-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 1324 of the DMD protein (p.Arg1324His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs768990357, ExAC 0.002%) but 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: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Stanford Center for Inherited Cardiovascular Disease,Stanford University RCV000786294 SCV000925056 uncertain significance not provided 2017-04-28 no assertion criteria provided provider interpretation p.Arg1324His (c.3971G>A) in exon 29 of the DMD gene (NM_004006.2) Given the lack of case data and lack of phenotype (HCM)-gene correlation, 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"). This variant has not been reported in the literature in association with DMD-associated disease. The arginine at codon 1324 is conserved across species. Neighboring amino acids are not conserved., as are neighboring amino acids. Another variant at this amino acid, p. Arg1324Cys, is present in ClinVar and is classified as either a variant of uncertain significance, likely benign, or benign. The p.Arg1324Cys variant has a MAF of 0.7% in the gnomAD database. The variant was reported online in 4 of 122,674 individuals (all female) 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, Ashkenazi, Latino descent. Specifically, the variant was observed in 2 of 26,545 chromosomes from people of Latino descent (MAF=0.007%), 1 of 79,777 chromosomes from people of European descent and 1 of 19,131 chromosomes from individuals of South Asian descent. The phenotype of those individuals is not publicly available. The dataset is comprised of multiple cohorts, some of which were recruited from the general population, others were enriched for common cardiovascular disease.

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