Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001037799 | SCV001201231 | likely pathogenic | Spastic paraplegia | 2019-03-15 | criteria provided, single submitter | clinical testing | 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. Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 29566793). Disruption of this splice site has been observed in several individuals affected with amyotrophic lateral sclerosis and to segregate with disease in families (PMID: 29342275, 29566793, 29954873). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 27 of the KIF5A gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. |