Submissions for variant NM_001365951.3(KIF1B):c.899A>G (p.Lys300Arg)

gnomAD frequency: 0.00009  dbSNP: rs373698346

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000167979	SCV000218627	uncertain significance	Charcot-Marie-Tooth disease type 2	2024-08-21	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 294 of the KIF1B protein (p.Lys294Arg). This variant is present in population databases (rs373698346, gnomAD 0.08%), 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 (CMT) disease (PMID: 25025039, 32376792; internal data). ClinVar contains an entry for this variant (Variation ID: 157531). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
Molecular Genetics Laboratory, London Health Sciences Centre	RCV000144876	SCV001336694	uncertain significance	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001530983	SCV001745904	likely benign	not provided	2021-03-01	criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV001530983	SCV002011648	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004019760	SCV002685204	likely benign	not specified	2020-09-02	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.
Fulgent Genetics, Fulgent Genetics	RCV005031650	SCV005662214	likely benign	Charcot-Marie-Tooth disease type 2A1; Neuroblastoma, susceptibility to, 1	2024-06-18	criteria provided, single submitter	clinical testing
Dept. of Medical Genetics, Telemark Hospital Trust, Telemark Hospital Trust	RCV000144876	SCV000172148	likely pathogenic	Charcot-Marie-Tooth disease	2013-11-01	no assertion criteria provided	research