ClinVar Miner

Submissions for variant NM_004321.7(KIF1A):c.206C>T (p.Ser69Leu) (rs786200949)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000693147 SCV000821003 pathogenic Spastic paraplegia 30, autosomal recessive; Hereditary sensory and autonomic neuropathy type IIC; Intellectual disability, autosomal dominant 9 2019-12-23 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 69 of the KIF1A protein (p.Ser69Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in an individual affected with uncomplicated hereditary spastic paraplegia (PMID: 25585697) and is reported to segregate with uncomplicated spastic paraplegia in a dominant fashion in families (PMID: 25585697, 26410750). ClinVar contains an entry for this variant (Variation ID: 188057). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000762334 SCV000892642 likely pathogenic not provided 2018-04-01 criteria provided, single submitter clinical testing
SIB Swiss Institute of Bioinformatics RCV001078152 SCV001426726 likely pathogenic Spastic paraplegia 30, autosomal recessive 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); Prevalence in affected individuals statistically increased over controls (PS4 downgraded to moderate); Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PP1 moderate); Assumed de novo, but no confirmation of paternity and maternity (PM6); 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);
Neuromuscular disorders lab,University of Helsinki RCV000167867 SCV000191086 pathogenic Hereditary spastic paraplegia 2014-10-27 no assertion criteria provided research
OMIM RCV001078152 SCV001244203 pathogenic Spastic paraplegia 30, autosomal recessive 2015-01-14 no assertion criteria provided literature only

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