ClinVar Miner

Submissions for variant NM_001244008.2(KIF1A):c.815A>G (p.Asn272Ser)

dbSNP: rs876661283
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000213797 SCV000279984 likely pathogenic not provided 2016-03-25 criteria provided, single submitter clinical testing The N272S variant in the KIF1A gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The N272S variant was not observed in approximately 6,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The N272S variant is a conservative amino acid substitution, which occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. The N272S variant is a strong candidate for a pathogenic variant, however, the possibility it may be a rare benign variant cannot be excluded.
Labcorp Genetics (formerly Invitae), Labcorp RCV001854764 SCV002124422 pathogenic Hereditary spastic paraplegia 30; Neuropathy, hereditary sensory, type 2C; Intellectual disability, autosomal dominant 9 2022-06-14 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 234899). This missense change has been observed in individual(s) with clinical features of KIF1A-related conditions (PMID: 33880452; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 272 of the KIF1A protein (p.Asn272Ser).

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