Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001923773 | SCV002196209 | uncertain significance | not provided | 2022-08-25 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1669 of the C5 protein (p.Glu1669Lys). This variant is present in population databases (rs758052311, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with C5-related conditions. ClinVar contains an entry for this variant (Variation ID: 1421436). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Fulgent Genetics, |
RCV002484556 | SCV002786894 | uncertain significance | Complement component 5 deficiency; Eculizumab, poor response to | 2021-07-07 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004603080 | SCV005095843 | uncertain significance | not specified | 2024-05-12 | criteria provided, single submitter | clinical testing | The c.5005G>A (p.E1669K) alteration is located in exon 41 (coding exon 41) of the C5 gene. This alteration results from a G to A substitution at nucleotide position 5005, causing the glutamic acid (E) at amino acid position 1669 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |