Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003556035 | SCV004292614 | pathogenic | not provided | 2023-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 485 of the GGCX protein (p.Arg485Pro). This variant is present in population databases (rs121909676, gnomAD 0.007%). This missense change has been observed in individual(s) with autosomal recessive vitamin K-dependent clotting factors deficiency (PMID: 15287948, 16905958, 34816548). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 16197). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects GGCX function (PMID: 27394683, 34816548). For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000017581 | SCV000037853 | pathogenic | Vitamin K-dependent clotting factors, combined deficiency of, type 1 | 2004-08-01 | no assertion criteria provided | literature only |