ClinVar Miner

Submissions for variant NM_021830.5(TWNK):c.1120C>T (p.Arg374Trp)

gnomAD frequency: 0.00001  dbSNP: rs267606682
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523637 SCV000618414 likely pathogenic not provided 2024-11-19 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25133958, 24091712, 20880070, 22353293, 31692161, 19513767, 18971204, 20479361, 34409151, 38703036)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000004892 SCV002598937 likely pathogenic Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 2022-09-27 criteria provided, single submitter clinical testing Variant summary: C10orf2 c.1120C>T (p.Arg374Trp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251374 control chromosomes (gnomAD). c.1120C>T has been reported in the literature in individuals affected with Progressive External Ophthalmoplegia, with confirmed segregation in two families (Echaniz-Laguna_2010), and in one individual with a positive family history suggesting autosomal dominant inheritance (Vandenberghe_2021). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter has assessed the variant since 2014: the variant was classified as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
OMIM RCV000004892 SCV000025068 pathogenic Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 2010-02-01 no assertion criteria provided literature only

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