Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Stellar |
RCV000505517 | SCV000599719 | pathogenic | Xeroderma pigmentosum, group C | 2017-06-19 | criteria provided, single submitter | clinical testing | The listed mutation in XPC gene was detected in affected child. The Illumina clinical exome sequencing panel was used and other genes involved in Xeroderma were free of pathogenic/ likely pathogenic variants. The affected child was homozygous for the mutation. The parents were then tested for this variant specifically and confirmed as heterozygous carriers. This variant was reported as pathogenic previously. |
| Counsyl | RCV000505517 | SCV000796473 | pathogenic | Xeroderma pigmentosum, group C | 2017-12-14 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV001090469 | SCV001246035 | pathogenic | not provided | 2018-10-01 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001175486 | SCV001339079 | pathogenic | Xeroderma pigmentosum | 2020-03-23 | criteria provided, single submitter | clinical testing | Variant summary: XPC c.1243C>T (p.Arg415X) 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 1.2e-05 in 249248 control chromosomes (gnomAD). c.1243C>T has been reported in the literature in multiple individuals affected with Xeroderma pigmentosum (Tamhankar_2015, Fassihi_2016). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Invitae | RCV001090469 | SCV001391401 | pathogenic | not provided | 2023-10-28 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg415*) 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 (rs757958943, gnomAD 0.007%). This premature translational stop signal has been observed in individuals with xeroderma pigmentosum (PMID: 26884178, 29178624). ClinVar contains an entry for this variant (Variation ID: 438623). For these reasons, this variant has been classified as Pathogenic. |
| 3billion | RCV000505517 | SCV002058246 | pathogenic | Xeroderma pigmentosum, group C | 2022-01-03 | criteria provided, single submitter | clinical testing | Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000438623, PMID:16081512). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000012, PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
| Baylor Genetics | RCV000505517 | SCV004207002 | pathogenic | Xeroderma pigmentosum, group C | 2023-04-28 | criteria provided, single submitter | clinical testing |