ClinVar Miner

Submissions for variant NM_004628.5(XPC):c.2152C>T (p.Arg718Ter)

dbSNP: rs754775337
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000666559 SCV000790867 likely pathogenic Xeroderma pigmentosum, group C 2017-04-12 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001280679 SCV001467977 pathogenic Xeroderma pigmentosum 2020-12-26 criteria provided, single submitter clinical testing Variant summary: XPC c.2152C>T (p.Arg718X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 249298 control chromosomes. c.2152C>T has been reported in the literature in individuals affected with Xeroderma Pigmentosum (example, Chavanne_2000, Zhang_2019). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in 10% of normal DNA repair activity (Chavanne_2000). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely pathogenic citing overlapping evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV001532474 SCV001748053 pathogenic not provided 2021-06-01 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000666559 SCV002020927 pathogenic Xeroderma pigmentosum, group C 2021-03-30 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001532474 SCV002161158 pathogenic not provided 2023-10-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg718*) in the XPC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in XPC are known to be pathogenic (PMID: 23173980, 25256075). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with xeroderma pigmentosum (PMID: 10766188, 30101995). ClinVar contains an entry for this variant (Variation ID: 551486). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000666559 SCV002804890 pathogenic Xeroderma pigmentosum, group C 2021-10-28 criteria provided, single submitter clinical testing

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