ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.3G>A (p.Met1Ile) (rs1021457619)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000814563 SCV000954976 pathogenic Arrhythmogenic right ventricular cardiomyopathy, type 10 2018-07-24 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the DSG2 mRNA. The next in-frame methionine is located at codon 179. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in an individual affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 20829228). A different variant (c.3G>C) giving rise to the same protein effect observed here (p.Met1?) has been observed to segregate with arrhythmogenic right ventricular cardiomyopathy in a family (PMID: 17105751), indicating that this residue may be critical for protein function. Variants that disrupt the p.Arg49 amino acid residue in DSG2 have been observed in affected individuals (PMID: 19151369). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001198464 SCV001369398 likely pathogenic mitochondrial 2019-07-12 criteria provided, single submitter clinical testing This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2. This variant was detected in heterozygous state.

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