ClinVar Miner

Submissions for variant NM_001365951.3(KIF1B):c.1346G>A (p.Ser449Asn)

gnomAD frequency: 0.00001  dbSNP: rs776678008
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001346678 SCV001540902 uncertain significance Charcot-Marie-Tooth disease type 2 2024-06-23 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 403 of the KIF1B protein (p.Ser403Asn). This variant is present in population databases (rs776678008, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with KIF1B-related conditions. ClinVar contains an entry for this variant (Variation ID: 1042686). 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%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Ambry Genetics RCV004036497 SCV002650200 likely benign not specified 2021-09-03 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.

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