ClinVar Miner

Submissions for variant NM_004321.7(KIF1A):c.760C>T (p.Arg254Trp) (rs879253888)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236491 SCV000292595 pathogenic not provided 2018-07-26 criteria provided, single submitter clinical testing The R254W variant in the KIF1A gene has been reported previously as de novo in a female with intellectual disability, cerebellar atrophy, lower limb spasticity and visual disturbance (Ohba et al., 2015). The R254W variant is not observed in large population cohorts (Lek et al., 2016). The R254W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. This substitution occurs at a position within the kinesin motor domain that is conserved across species (Citterio et al., 2015). In silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant in the same residue (R254Q) has been reported as de novo in an individual who also had cerebellar ataxia, spasticity in the lower limbs and muscle weakness, supporting the functional importance of this region of the protein (Ohba et al., 2015). Therefore, we interpret R254W as a pathogenic variant
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000236491 SCV000700740 pathogenic not provided 2017-06-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV000623278 SCV000741095 pathogenic Inborn genetic diseases 2016-02-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
Fulgent Genetics,Fulgent Genetics RCV000763486 SCV000894271 likely pathogenic Hereditary sensory and autonomic neuropathy type IIA; Spastic paraplegia 30, autosomal recessive; Hereditary sensory and autonomic neuropathy type IIC; Mental retardation, autosomal dominant 9 2018-10-31 criteria provided, single submitter clinical testing
Institute of Human Genetics,Klinikum rechts der Isar RCV000995795 SCV001150146 pathogenic Mental retardation, autosomal dominant 9 2018-01-30 criteria provided, single submitter clinical testing

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