Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001390773 | SCV001592614 | pathogenic | not provided | 2024-01-04 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln19*) in the C5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in C5 are known to be pathogenic (PMID: 7730648, 19414197, 27026170). This variant is present in population databases (rs121909587, gnomAD 0.1%). This premature translational stop signal has been observed in individual(s) with C5 deficiency and C5 deficiency in a family and has also been reported in individuals affected with C5 deficiency, including in the compound heterozygous state (PMID: 7730648, 23371790, 25534848). It has also been observed to segregate with disease in related individuals. This variant is also known as p.Q1X. ClinVar contains an entry for this variant (Variation ID: 17050). For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV001535994 | SCV001752667 | pathogenic | Complement component 5 deficiency; Eculizumab, poor response to | 2021-06-30 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000018578 | SCV003834805 | pathogenic | Complement component 5 deficiency | 2022-12-16 | criteria provided, single submitter | clinical testing | |
| Laboratory for Molecular Medicine, |
RCV000018578 | SCV004848103 | pathogenic | Complement component 5 deficiency | 2017-07-28 | criteria provided, single submitter | clinical testing | The p.Gln19X variant in C5 has been reported in 3 families with C5 complement deficiency. In 1 family, the 2 affected members carried the variant in the homozygous state (Arnaout 2013), whereas in the remaining 2 families (Wang 1995, reported as(C84 AG to TAG) ) the variant was found in the heterozygous state in 6 affected individuals (presumably a second undetected variant was present on the other allele) . This variant has also been identified in 0.12% (29/24,032) of African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs121909587). This nonsense variant leads to a premature termination codon at position 19, which is predicted to lead to a truncated or absent protein. In summary, this variant meets criteria to be classified as pathogenic for C5 complement deficiency in an autosomal recessive manner based upon biallelic case observations, segregation studies and the nature of the variant (nonsense). |
| Center for Genomic Medicine, |
RCV004018641 | SCV005016545 | pathogenic | Lathosterolosis | 2024-03-14 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000018578 | SCV000038861 | pathogenic | Complement component 5 deficiency | 1995-05-15 | no assertion criteria provided | literature only |