ClinVar Miner

Submissions for variant NM_001354975.1(XPA):c.218_222CTTAT[1] (p.Leu75fs) (rs1200172747)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000001049 SCV000794422 pathogenic Xeroderma pigmentosum, type 1 2017-09-26 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000780797 SCV000918359 pathogenic Xeroderma pigmentosum 2018-05-11 criteria provided, single submitter clinical testing Variant summary: XPA c.349_353delCTTAT (p.Leu117GlufsX4) 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 7.2e-06 in 276628 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in XPA causing Xeroderma Pigmentosum (7.2e-06 vs 1.60e-03), allowing no conclusion about variant significance. The variant, c.349_353delCTTAT, has been reported in the literature in individuals affected with Xeroderma Pigmentosum (Ghafouri-Fard_2016, Christen-Zaech_2009, States_1998) where it was found to co-segregate with disease. These data indicate that the variant is likely to be associated with disease. At-least one study reports a hypersensitivity of patient derived fibroblasts to the killing effects of UV radiation, although quantitative data were not provided by the authors. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000001049 SCV000021199 pathogenic Xeroderma pigmentosum, type 1 1992-03-01 no assertion criteria provided literature only

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