Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000000283 | SCV000788549 | pathogenic | Xeroderma pigmentosum, group C | 2017-12-29 | criteria provided, single submitter | clinical testing | |
| Medical Molecular Genetics Department, |
RCV000000283 | SCV001335287 | pathogenic | Xeroderma pigmentosum, group C | 2015-12-01 | criteria provided, single submitter | research | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001260295 | SCV001437210 | pathogenic | Xeroderma pigmentosum | 2020-09-25 | criteria provided, single submitter | clinical testing | Variant summary: XPC c.1735C>T (p.Arg579X) 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. 4/4 computational tools predict no significant impact on normal splicing. However, at least two publications experimental evidence that this variant affects mRNA splicing and results in the deletion of 3 end of exon 8. The variant allele was found at a frequency of 1.2e-05 in 249312 control chromosomes (gnomAD). c.1735C>T has been reported in the literature in individuals affected with Xeroderma Pigmentosum (Chavanne_2000, Gozukara_2001, Masaki_2018). These data indicate that the variant is likely to be associated with disease. At least two publications report experimental evidence evaluating an impact on protein function and results in DNA repair defect (Chavanne_2000, Gozukara_2001). Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Labcorp Genetics |
RCV001851508 | SCV002246533 | pathogenic | not provided | 2023-08-22 | criteria provided, single submitter | clinical testing | This premature translational stop signal has been observed in individuals with xeroderma pigmentosum (PMID: 10766188, 11511294, 25256075, 29330851). It has also been observed to segregate with disease in related individuals. This variant is also known as Arg579opal. ClinVar contains an entry for this variant (Variation ID: 259). For these reasons, this variant has been classified as Pathogenic. This variant is present in population databases (rs121965088, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Arg579*) 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, |
RCV000000283 | SCV002788476 | pathogenic | Xeroderma pigmentosum, group C | 2021-08-12 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000000283 | SCV004206999 | pathogenic | Xeroderma pigmentosum, group C | 2023-05-12 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001851508 | SCV005202021 | pathogenic | not provided | 2023-09-01 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Published functional studies demonstrate loss-of-function of nucleotide excision repair (Bernardes de Jesus et al., 2008); This variant is associated with the following publications: (PMID: 29330851, 32239545, 25525159, 29356054, 31589614, 33077847, 10766188, 18809580, 33672602) |
| OMIM | RCV000000283 | SCV000020427 | pathogenic | Xeroderma pigmentosum, group C | 2001-08-01 | no assertion criteria provided | literature only |