ClinVar Miner

Submissions for variant NM_004628.4(XPC):c.2074A>T (p.Lys692Ter) (rs374117852)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000589424 SCV000698490 pathogenic Xeroderma pigmentosum 2017-04-06 criteria provided, single submitter clinical testing Variant summary: The XPC c.2074A>T (p.Lys692*) 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. These predictions were confirmed by Khan et al (2006) who showed severely reduced level of mRNA and lack of protein expression in in vitro assay. This variant was found in 1/108904 control chromosomes at a frequency of 0.0000092, which does not exceed the estimated maximal expected allele frequency of a pathogenic XPC variant (0.0014142). This variant has been reported in at least two unrelated patients with Xeroderma Pigmentosum (Khan_2006, Kuschal_2013). In addition, truncation variants downstream of this position, such as c.2152C>T (p.R718*), c.2262delC (p.Asn754Lysfs) and c.2251-1G>C have been classified as "Pathogenic" by reputable databases/diagnostic laboratories . Taken together, this variant is classified as Pathogenic.
Counsyl RCV000666668 SCV000790997 likely pathogenic Xeroderma pigmentosum, group C 2017-04-18 no assertion criteria provided clinical testing

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