Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000674100 | SCV000799376 | pathogenic | Xeroderma pigmentosum group A | 2018-04-16 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV000674100 | SCV000894458 | pathogenic | Xeroderma pigmentosum group A | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001194216 | SCV001363573 | pathogenic | Xeroderma pigmentosum | 2021-11-10 | criteria provided, single submitter | clinical testing | Variant summary: XPA c.331G>T (p.Glu111X) 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 250654 control chromosomes (gnomAD). c.331G>T has been reported in the literature in multiple individuals affected with Xeroderma pigmentosum (Amr_2014, Messaoud_2012, Zhou_2017). 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. Three ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Labcorp Genetics |
RCV001230906 | SCV001403406 | pathogenic | not provided | 2023-07-27 | criteria provided, single submitter | clinical testing | This premature translational stop signal has been observed in individuals with xeroderma pigmentosum (PMID: 22081045, 27607234). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 557900). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. This variant is present in population databases (rs769255883, gnomAD 0.02%). This sequence change creates a premature translational stop signal (p.Glu111*) in the XPA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in XPA are known to be pathogenic (PMID: 27607234). |
| Kasturba Medical College, |
RCV000674100 | SCV002053806 | pathogenic | Xeroderma pigmentosum group A | criteria provided, single submitter | clinical testing | ||
| Baylor Genetics | RCV000674100 | SCV004206959 | pathogenic | Xeroderma pigmentosum group A | 2023-01-27 | criteria provided, single submitter | clinical testing |