Submissions for variant NM_001244008.2(KIF1A):c.232G>A (p.Gly78Ser)

dbSNP: rs1057518760

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
SIB Swiss Institute of Bioinformatics	RCV001251219	SCV001426708	likely pathogenic	Hereditary spastic paraplegia 30	2020-06-15	criteria provided, single submitter	curation	This variant is interpreted as likely pathogenic for spastic paraplegia 30, autosomal dominant. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); De novo (paternity and maternity confirmed) (PS2 downgraded to moderate); Multiple lines of computational evidence support a deleterious effect on the gene or gene product (PP3); Missense variant in a gene that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease (PP2).
Paris Brain Institute, Inserm - ICM	RCV001251219	SCV001451078	pathogenic	Hereditary spastic paraplegia 30		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001861441	SCV002167160	pathogenic	Hereditary spastic paraplegia 30; Neuropathy, hereditary sensory, type 2C; Intellectual disability, autosomal dominant 9	2022-08-16	criteria provided, single submitter	clinical testing	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. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 373905). This missense change has been observed in individual(s) with autosomal dominant hereditary spastic paraplegia (PMID: 31488895). 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 glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 78 of the KIF1A protein (p.Gly78Ser).
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001251219	SCV005400661	likely pathogenic	Hereditary spastic paraplegia 30	2024-11-19	criteria provided, single submitter	clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000414911	SCV000492532	likely pathogenic	Hyperreflexia; Clonus; Lower limb hyperreflexia; Spastic paraplegia	2016-04-18	no assertion criteria provided	clinical testing