Total submissions: 6
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, |
RCV000760166 | SCV000889984 | uncertain significance | Charcot-Marie-Tooth disease type 2A1 | 2018-03-16 | criteria provided, single submitter | research | |
Molecular Genetics Laboratory, |
RCV001174207 | SCV001337333 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
Mayo Clinic Laboratories, |
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. |
Ce |
RCV001507419 | SCV003916047 | uncertain significance | not provided | 2023-02-01 | criteria provided, single submitter | clinical testing |