ClinVar Miner

Submissions for variant NM_004006.3(DMD):c.818A>G (p.His273Arg)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002644080 SCV003521627 uncertain significance Duchenne muscular dystrophy 2024-12-04 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 273 of the DMD protein (p.His273Arg). 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: 2200247). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
Ambry Genetics RCV003162078 SCV003853636 uncertain significance Cardiovascular phenotype 2022-11-28 criteria provided, single submitter clinical testing The p.H273R variant (also known as c.818A>G), located in coding exon 8 of the DMD gene, results from an A to G substitution at nucleotide position 818. The histidine at codon 273 is replaced by arginine, an amino acid with highly similar properties. Based on data from gnomAD, the G allele has an overall frequency of 0.0005% (1/182868) total alleles studied, with no hemizygotes observed. The highest observed frequency was 0.0076% (1/13153) of African/African American alleles. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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