ClinVar Miner

Submissions for variant NM_004006.3(DMD):c.1586T>C (p.Leu529Ser)

gnomAD frequency: 0.00003  dbSNP: rs889238270
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000705601 SCV000834606 likely benign Duchenne muscular dystrophy 2024-05-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001192550 SCV001360769 uncertain significance not specified 2019-06-14 criteria provided, single submitter clinical testing Variant summary: DMD c.1586T>C (p.Leu529Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 5.5e-06 in 182873 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1586T>C in individuals affected with Duchenne muscular dystrophy and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
GeneDx RCV001766557 SCV001990817 uncertain significance not provided 2019-04-01 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 581693; Landrum et al., 2016); Missense variant in a gene in which most reported pathogenic variants are truncating/loss-of-function; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect
Ambry Genetics RCV002397479 SCV002705986 uncertain significance Cardiovascular phenotype 2022-04-07 criteria provided, single submitter clinical testing The p.L529S variant (also known as c.1586T>C), located in coding exon 13 of the DMD gene, results from a T to C substitution at nucleotide position 1586. The leucine at codon 529 is replaced by serine, an amino acid with dissimilar properties. Based on data from gnomAD, the C allele has an overall frequency of 0.0005% (1/182873) total alleles studied, with 1 hemizygote observed. The highest observed frequency was 0.0037% (1/27387) of Latino/ Admixed American alleles. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001835931 SCV002090348 uncertain significance Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency 2018-11-08 no assertion criteria provided clinical testing

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