ClinVar Miner

Submissions for variant NM_004321.7(KIF1A):c.646C>T (p.Arg216Cys) (rs797045164)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Child and Family Research Institute RCV000207243 SCV000243779 pathogenic PEHO syndrome 2015-08-07 criteria provided, single submitter literature only
Invitae RCV000191020 SCV000651706 pathogenic Intellectual disability, autosomal dominant 9 2017-03-16 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 216 of the KIF1A protein (p.Arg216Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (rs797045164, ExAC no frequency). This variant has been shown to arise de novo in an individual affected with progressive encephalopathy and brain atrophy leading to autosomal dominant complicated hereditary spastic paraplegia (PMID: 26125038). Experimental studies have shown that this missense change abolishes KIF1A motility in vitro (PMID: 26125038). A different missense substitution at this codon (p.Arp216His) has been determined to be pathogenic (PMID: 26125038). This suggests that the arginine residue is critical for KIF1A protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000191020 SCV000245998 pathogenic Intellectual disability, autosomal dominant 9 2015-06-01 no assertion criteria provided literature only

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