Submissions for variant NM_001365951.3(KIF1B):c.3407T>C (p.Ile1136Thr)

gnomAD frequency: 0.00009  dbSNP: rs374098797

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001065481	SCV001230439	uncertain significance	Charcot-Marie-Tooth disease type 2	2024-07-30	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1090 of the KIF1B protein (p.Ile1090Thr). This variant is present in population databases (rs374098797, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (PMID: 32376792). ClinVar contains an entry for this variant (Variation ID: 155749). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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	RCV001173597	SCV001336697	uncertain significance	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004019754	SCV002612486	likely benign	not specified	2020-09-15	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.
Revvity Omics, Revvity	RCV003485542	SCV003814567	uncertain significance	Charcot-Marie-Tooth disease type 2A1	2021-12-28	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV005042280	SCV005676311	uncertain significance	Charcot-Marie-Tooth disease type 2A1; Neuroblastoma, susceptibility to, 1	2024-06-05	criteria provided, single submitter	clinical testing
Northcott Neuroscience Laboratory, ANZAC Research Institute	RCV000143820	SCV000188714	non-pathogenic	not provided		no assertion criteria provided	not provided	Converted during submission to Benign.