ClinVar Miner

Submissions for variant NM_004006.3(DMD):c.6799C>A (p.Leu2267Ile)

gnomAD frequency: 0.00005  dbSNP: rs758654750
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520793 SCV000620081 uncertain significance not provided 2017-08-15 criteria provided, single submitter clinical testing The L2267I variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The L2267I variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Labcorp Genetics (formerly Invitae), Labcorp RCV000552438 SCV000625943 likely benign Duchenne muscular dystrophy 2024-12-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV002367742 SCV002666279 uncertain significance Cardiovascular phenotype 2021-11-22 criteria provided, single submitter clinical testing The p.L2267I variant (also known as c.6799C>A), located in coding exon 47 of the DMD gene, results from a C to A substitution at nucleotide position 6799. The leucine at codon 2267 is replaced by isoleucine, an amino acid with highly similar properties. Based on data from gnomAD, the A allele has an overall frequency of 0.0020% (4/205017) total alleles studied, with 1 hemizygote(s) observed. The highest observed frequency was 0.0032% (3/92573) of European (non-Finnish) alleles. This amino acid position is highly 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004800443 SCV005422800 uncertain significance not specified 2024-10-17 criteria provided, single submitter clinical testing Variant summary: DMD c.6799C>A (p.Leu2267Ile) results in a conservative amino acid change located in the spectrin repeat region (IPR002017) of encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.1e-05 in 183123 control chromosomes (gnomAD v2.1), including 1 hemizygote. 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.6799C>A in individuals affected with Duchenne Muscular Dystrophy and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 451387). Based on the evidence outlined above, the variant was classified as uncertain significance.
Natera, Inc. RCV001835837 SCV002087822 uncertain significance Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency 2018-06-12 no assertion criteria provided clinical testing

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