Submissions for variant NM_001244008.2(KIF1A):c.75G>C (p.Lys25Asn)

gnomAD frequency: 0.00001  dbSNP: rs768320178

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000398114	SCV000429337	uncertain significance	Hereditary sensory and autonomic neuropathy type 2	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000310159	SCV000429338	uncertain significance	Spastic Paraplegia, Recessive	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000343962	SCV000429339	uncertain significance	Intellectual Disability, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001861148	SCV002298380	uncertain significance	Hereditary spastic paraplegia 30; Neuropathy, hereditary sensory, type 2C; Intellectual disability, autosomal dominant 9	2024-08-14	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 25 of the KIF1A protein (p.Lys25Asn). This variant is present in population databases (rs768320178, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with KIF1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 335286). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt KIF1A protein function with a positive predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.