ClinVar Miner

Submissions for variant NM_001365951.3(KIF1B):c.2159C>T (p.Thr720Ile)

gnomAD frequency: 0.00024  dbSNP: rs41274468
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000467791 SCV000547914 uncertain significance Charcot-Marie-Tooth disease type 2 2023-12-12 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 674 of the KIF1B protein (p.Thr674Ile). This variant is present in population databases (rs41274468, gnomAD 0.03%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 29590070, 32376792). ClinVar contains an entry for this variant (Variation ID: 408312). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt KIF1B protein function with a negative predictive value of 80%. 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.
Center for Precision Medicine, Vanderbilt University Medical Center RCV000760166 SCV000889984 uncertain significance Charcot-Marie-Tooth disease type 2A1 2018-03-16 criteria provided, single submitter research
Molecular Genetics Laboratory, London Health Sciences Centre RCV001174207 SCV001337333 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001507419 SCV001712962 uncertain significance not provided 2020-10-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV004022688 SCV002723774 likely benign not specified 2020-07-06 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen RCV001507419 SCV003916047 uncertain significance not provided 2023-02-01 criteria provided, single submitter clinical testing

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