ClinVar Miner

Submissions for variant NM_006612.6(KIF1C):c.3121C>T (p.Arg1041Trp)

gnomAD frequency: 0.00003  dbSNP: rs200388087
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001300848 SCV001489998 uncertain significance Spastic ataxia 2 2022-04-18 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1041 of the KIF1C protein (p.Arg1041Trp). This variant is present in population databases (rs200388087, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with KIF1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 1004180). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001847234 SCV002105330 uncertain significance Hereditary spastic paraplegia 2019-05-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV001300848 SCV002779583 uncertain significance Spastic ataxia 2 2022-04-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV003166690 SCV003862375 uncertain significance Inborn genetic diseases 2023-02-10 criteria provided, single submitter clinical testing The c.3121C>T (p.R1041W) alteration is located in exon 23 (coding exon 21) of the KIF1C gene. This alteration results from a C to T substitution at nucleotide position 3121, causing the arginine (R) at amino acid position 1041 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004770015 SCV005380783 uncertain significance not specified 2024-08-09 criteria provided, single submitter clinical testing Variant summary: KIF1C c.3121C>T (p.Arg1041Trp) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00016 in 219074 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in KIF1C causing Spastic Ataxia 2, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.3121C>T in individuals affected with Spastic Ataxia 2 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1004180). Based on the evidence outlined above, the variant was classified as uncertain significance.

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