Submissions for variant NM_004523.4(KIF11):c.1280del (p.Gly427fs)

dbSNP: rs1589600660

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001008939	SCV001168746	likely pathogenic	not provided	2018-07-16	criteria provided, single submitter	clinical testing	The c.1280delG variant in the KIF11gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.1280delG variant causes a frameshift starting with codon Glycine 427, changes this amino acid to a Valine residue, and creates a premature Stop codon at position 7 of the new reading frame, denoted p.Gly427ValfsX7. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1280delG variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.1280delG as a likely pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001008939	SCV004469187	pathogenic	not provided	2023-05-22	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gly427Valfs*7) in the KIF11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KIF11 are known to be pathogenic (PMID: 22284827, 24281367). This variant has not been reported in the literature in individuals affected with KIF11-related conditions. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 817728).