Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000665434 | SCV000789559 | pathogenic | Xeroderma pigmentosum, group C | 2017-02-08 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001049994 | SCV001214080 | pathogenic | not provided | 2022-09-05 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 550638). This variant is also known as 4 del TGAG 525–8. This premature translational stop signal has been observed in individual(s) with xeroderma pigmentosum (PMID: 16081512, 27387384). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Glu141Leufs*6) 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). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001194079 | SCV001363339 | pathogenic | Xeroderma pigmentosum | 2019-08-19 | criteria provided, single submitter | clinical testing | Variant summary: XPC c.420_423delTGAG (p.Glu141LeufsX6) 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 (c.463C>T, p.Arg155X; c.566_567delAT, p.Tyr189fsX10; c.1103_1104delAA, p.Gln368fsX6). The variant allele was found at a frequency of 4e-06 in 249086 control chromosomes (gnomAD). The variant, c.420_423delTGAG, has been reported in the literature in individuals in (homozygous and compound heterozygous state) affected with Xeroderma pigmentosum (Khan_2006, Schubert_2016). These data indicate that the variant may be associated with disease. At least one publication, Schubert_2016, analyzed post-UV cell survival and qRT-PCR for this variant and reports variant effect results in 10%-<30% of normal activity. 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. |
| Baylor Genetics | RCV000665434 | SCV004206970 | pathogenic | Xeroderma pigmentosum, group C | 2023-09-24 | criteria provided, single submitter | clinical testing | |
| Laboratory of Diagnostic Genome Analysis, |
RCV001049994 | SCV001797949 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
| Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV001049994 | SCV001968469 | pathogenic | not provided | no assertion criteria provided | clinical testing |