Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002531121 | SCV003461635 | likely pathogenic | Spastic paraplegia | 2022-08-21 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1007 of the KIF5A protein (p.Arg1007Gly). RNA analysis indicates that this missense change induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with KIF5A-related conditions (PMID: 29342275; Invitae). ClinVar contains an entry for this variant (Variation ID: 504479). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Studies have shown that this missense change results in skipping of exon 27 and introduces a premature termination codon (PMID: 29342275). The resulting mRNA is expected to undergo nonsense-mediated decay. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Ce |
RCV003311856 | SCV004010172 | likely pathogenic | not provided | 2023-05-01 | criteria provided, single submitter | clinical testing | KIF5A: PM2, PM5, PS4:Moderate, PP1, PS3:Supporting |
| OMIM | RCV000598752 | SCV000710803 | risk factor | Amyotrophic lateral sclerosis, susceptibility to, 25 | 2022-11-23 | no assertion criteria provided | literature only |