ClinVar Miner

Submissions for variant NM_001244008.2(KIF1A):c.715G>A (p.Glu239Lys)

gnomAD frequency: 0.00004  dbSNP: rs1231775359
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001211242 SCV001382770 uncertain significance Hereditary spastic paraplegia 30; Neuropathy, hereditary sensory, type 2C; Intellectual disability, autosomal dominant 9 2024-07-14 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 239 of the KIF1A protein (p.Glu239Lys). This variant is present in population databases (no rsID available, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of hereditary sensory and autonomic neuropathy (PMID: 35132656). ClinVar contains an entry for this variant (Variation ID: 941458). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KIF1A protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects KIF1A function (PMID: 35132656). 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.
PreventionGenetics, part of Exact Sciences RCV004738192 SCV005344626 uncertain significance KIF1A-related disorder 2024-05-23 no assertion criteria provided clinical testing The KIF1A c.715G>A variant is predicted to result in the amino acid substitution p.Glu239Lys. This variant was reported in an individual with Charcot-Marie-Tooth disease, type 2 and in vitro studies showed that this variant defect the function of the protein (Morikawa et al 2022. PubMed ID: 35132656). This variant is reported in 0.011% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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