ClinVar Miner

Submissions for variant NM_001354730.1(XPC):c.1626+13TG[2] (rs754532049)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Claritas Genomics RCV000000286 SCV000222868 pathogenic Xeroderma pigmentosum, group C 2015-03-18 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781925 SCV000920351 pathogenic Xeroderma pigmentosum 2017-10-19 criteria provided, single submitter clinical testing Variant summary: The XPC c.1643_1644delTG (p.Val548AlafsX25) variant results in a premature termination codon, predicted to cause a truncated or absent XPC protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. Functional studies showed absence of XPC protein expression in lymphoblasts from XP patients and reduced post-UV unscheduled DNA synthesis (Khan_2006). This variant was found in 5/246258 control chromosomes at a frequency of 0.0000203, which does not exceed the estimated maximal expected allele frequency of a pathogenic XPC variant (0.0014142). This variant is considered a founder mutation and is reported in 87% of XP-C cases from North Africa (Bensenouci_2016, El-Harith_2012, Khan_2006). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000791609 SCV000930867 pathogenic not provided 2018-12-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val548Alafs*25) in the XPC gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs754532049, ExAC 0.001%). This variant has been observed in many individuals with xeroderma pigmentosum and is a common founder mutation among individuals of North African ancestry (PMID: 20054342, 23143338, 27413738). ClinVar contains an entry for this variant (Variation ID: 262). Loss-of-function variants in XPC are known to be pathogenic (PMID: 23173980, 25256075). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000000286 SCV000020430 pathogenic Xeroderma pigmentosum, group C 2009-07-01 no assertion criteria provided literature only
GeneReviews RCV000000286 SCV000320723 pathogenic Xeroderma pigmentosum, group C 2016-09-26 no assertion criteria provided literature only

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