Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000498777 | SCV000589668 | uncertain significance | not provided | 2018-09-28 | criteria provided, single submitter | clinical testing | The E755K variant in the KIF5A gene has been reported previously in a patient of HSP and this individual's father who displayed subclinical signs of HSP; however, not all genes associated with HSP were evaluated in this study (Crimella et al., 2012). The E755K variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The E755K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret E755K as a variant of uncertain significance. |
| Labcorp Genetics |
RCV001852613 | SCV002264479 | likely benign | Spastic paraplegia | 2024-11-25 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004525859 | SCV005039316 | uncertain significance | not specified | 2024-03-29 | criteria provided, single submitter | clinical testing | Variant summary: KIF5A c.2263G>A (p.Glu755Lys) results in a conservative amino acid change located in the stalk domain (Crimella_2012) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251394 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2263G>A has been reported in the literature in individuals affected with KIF5A-Related Disorders (Crimella_2012, Simone_2018, Du_2020, Grassano_2021). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 21623771, 33155544, 35896380, 33208543, 30581417). ClinVar contains an entry for this variant (Variation ID: 37128). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| OMIM | RCV000030759 | SCV000053420 | pathogenic | Hereditary spastic paraplegia 10 | 2012-08-01 | no assertion criteria provided | literature only |