Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000319934 | SCV000380444 | likely benign | Hereditary spastic paraplegia 10 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. |
| ARUP Laboratories, |
RCV001812799 | SCV001474013 | uncertain significance | not provided | 2023-10-26 | criteria provided, single submitter | clinical testing | The KIF5A c.1932G>A, p.Thr644Thr variant (rs370644634), to our knowledge, has not been reported in the medical literature; however, this variant is listed in the ClinVar database (Variation ID: 309941). This variant is found in the general population with an overall allele frequency of 0.003% (10/282,866 alleles) in the Genome Aggregation Database. This variant does not alter the primary amino acid sequence of KIF5A; however, splice site prediction algorithms predict this variant may activate a cryptic splice acceptor. Although, without functional evidence, such predictions are not sufficient to assign pathogenicity. Thus, based on the available information, the clinical significance of this variant is uncertain. |
| Invitae | RCV001306129 | SCV001495488 | likely benign | Spastic paraplegia | 2024-01-24 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV003391112 | SCV004119506 | uncertain significance | KIF5A-related condition | 2023-01-06 | criteria provided, single submitter | clinical testing | The KIF5A c.1932G>A variant is not predicted to result in an amino acid change (p.=). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.025% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-57969449-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |