ClinVar Miner

Submissions for variant NM_004321.7(KIF1A):c.4624G>A (p.Asp1542Asn) (rs200141437)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000195190 SCV000247731 uncertain significance not specified 2015-05-15 criteria provided, single submitter clinical testing
GeneDx RCV000195190 SCV000279663 uncertain significance not specified 2017-03-10 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the KIF1A gene. The D1542N variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The D1542N variant is observed in 32/64558 alleles (0.1%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The D1542N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position where amino acids with similar properties to Aspartic acid are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. This amino acid substitution does not occur within the predicted motor domain of the protein, where all pathogenic missense KIF1A pathogenic variants have been identified to-date (Lee et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000513801 SCV000610069 uncertain significance not provided 2017-08-01 criteria provided, single submitter clinical testing
Invitae RCV000538003 SCV000638628 uncertain significance Spastic paraplegia 30, autosomal recessive; Hereditary sensory and autonomic neuropathy type IIC; Mental retardation, autosomal dominant 9 2018-12-21 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 1542 of the KIF1A protein (p.Asp1542Asn). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs200141437, ExAC 0.05%). This variant has not been reported in the literature in individuals with KIF1A-related disease. ClinVar contains an entry for this variant (Variation ID: 211292). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000513801 SCV000892639 uncertain significance not provided 2018-09-30 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764392 SCV000895445 uncertain significance 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

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