ClinVar Miner

Submissions for variant NM_004628.5(XPC):c.1103_1104del (p.Gln368fs)

gnomAD frequency: 0.00002  dbSNP: rs1450238352
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000671910 SCV000796943 pathogenic Xeroderma pigmentosum, group C 2018-01-05 criteria provided, single submitter clinical testing
Medical Molecular Genetics Department, National Research Center RCV000671910 SCV001335288 pathogenic Xeroderma pigmentosum, group C 2015-12-01 criteria provided, single submitter research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001194078 SCV001363338 pathogenic Xeroderma pigmentosum 2019-01-24 criteria provided, single submitter clinical testing Variant summary: XPC c.1103_1104delAA (p.Gln368ArgfsX6) 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 allele was found at a frequency of 6.5e-05 in 30946 control chromosomes (gnomAD). c.1103_1104delAA has been reported in the literature in multiple compound heterozygous and homozygous individuals affected with Xeroderma Pigmentosum (Chavanne 2000, Khan 2006, Schubert 2016). These data indicate that the variant is very likely to be associated with disease. These publications also reported experimental evidence evaluating an impact on protein function, demonstrating strongly decreased mRNA levels, absence of the protein and deficient repair synthesis and/or cell survival after UV-irradiation. The most pronounced variant effect results in <10% of normal activity. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001390106 SCV001591728 pathogenic not provided 2023-03-19 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 267279). This premature translational stop signal has been observed in individual(s) with xeroderma pigmentosum (PMID: 10766188). This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Gln368Argfs*6) 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).
Fulgent Genetics, Fulgent Genetics RCV000671910 SCV002815230 pathogenic Xeroderma pigmentosum, group C 2021-07-02 criteria provided, single submitter clinical testing
Baylor Genetics RCV000671910 SCV004206997 pathogenic Xeroderma pigmentosum, group C 2023-11-15 criteria provided, single submitter clinical testing

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