ClinVar Miner

Submissions for variant NM_004006.3(DMD):c.4467A>C (p.Glu1489Asp)

gnomAD frequency: 0.00004  dbSNP: rs373162382
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000528126 SCV000625901 uncertain significance Duchenne muscular dystrophy 2022-05-20 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 1489 of the DMD protein (p.Glu1489Asp). This variant is present in population databases (rs373162382, gnomAD 0.005%). 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: 455898). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 RCV002330825 SCV002638853 uncertain significance Cardiovascular phenotype 2023-03-24 criteria provided, single submitter clinical testing The p.E1489D variant (also known as c.4467A>C), located in coding exon 32 of the DMD gene, results from an A to C substitution at nucleotide position 4467. The glutamic acid at codon 1489 is replaced by aspartic acid, an amino acid with highly similar properties. Based on data from gnomAD, the C allele has an overall frequency of <0.01% (20/200505) total alleles studied, with 0 hemizygote(s) observed. The highest observed frequency was <0.01% (1/19077) of African alleles. This amino acid position is not well conserved in available vertebrate species, and aspartic acid is the reference amino acid in other 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.
Natera, Inc. RCV001835843 SCV002085320 uncertain significance Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency 2018-06-22 no assertion criteria provided clinical testing

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