ClinVar Miner

Submissions for variant NM_004321.7(KIF1A):c.773C>T (p.Thr258Met) (rs1553638086)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000548642 SCV000638638 pathogenic Spastic paraplegia 30, autosomal recessive; Hereditary sensory and autonomic neuropathy type IIC; Intellectual disability, autosomal dominant 9 2020-01-03 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 258 of the KIF1A protein (p.Thr258Met). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with hereditary spastic paraplegia (HSP) in a family (PMID: 28970574). This variant has also been observed to be de novo in an individual with clinical features of HSP (Invitae). ClinVar contains an entry for this variant (Variation ID: 464261). This variant has been reported to affect KIF1A protein function (PMID: 28970574). For these reasons, this variant has been classified as Pathogenic.
SIB Swiss Institute of Bioinformatics RCV001251233 SCV001426732 pathogenic Spastic paraplegia 30, autosomal recessive 2020-06-15 criteria provided, single submitter curation This variant is interpreted as 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); 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); Multiple lines of computational evidence support a deleterious effect on the gene or gene product (PP3); De novo (paternity and maternity confirmed) (PS2); Prevalence in affected individuals statistically increased over controls (PS4 downgraded to supporting); Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PP1).

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