Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000664637 | SCV000788635 | pathogenic | Xeroderma pigmentosum, group C | 2017-12-29 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001201195 | SCV001372265 | pathogenic | Xeroderma pigmentosum | 2020-06-26 | criteria provided, single submitter | clinical testing | Variant summary: XPC c.658C>T (p.Arg220X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 2e-05 in 247090 control chromosomes. c.658C>T has been reported in the literature in multiple individuals affected with Xeroderma Pigmentosum and has also been subsequently cited by others (example, Chavanne_2000, Soufir_2010, Hadj-Rabia_2013, Fassihi_2016, McDaniel_2007, Rivera-Begeman_2007). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function (Chavanne_2000). The most pronounced variant effect results in <10% of normal activity in repair synthesis ability. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Labcorp Genetics |
RCV001385310 | SCV001585124 | pathogenic | not provided | 2024-01-08 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg220*) 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 present in population databases (rs745679643, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with xeroderma pigmentosum (PMID: 10766188). ClinVar contains an entry for this variant (Variation ID: 550020). For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV000664637 | SCV004206984 | pathogenic | Xeroderma pigmentosum, group C | 2024-03-18 | criteria provided, single submitter | clinical testing |