ClinVar Miner

Submissions for variant NM_001365951.3(KIF1B):c.5203A>G (p.Ser1735Gly)

gnomAD frequency: 0.00003  dbSNP: rs775692548
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001060670 SCV001225374 uncertain significance Charcot-Marie-Tooth disease type 2 2023-06-11 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 855407). This variant has not been reported in the literature in individuals affected with KIF1B-related conditions. This variant is present in population databases (rs775692548, gnomAD 0.02%). This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 1689 of the KIF1B protein (p.Ser1689Gly).
Ambry Genetics RCV004031927 SCV002642761 likely benign not specified 2020-09-29 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 RCV003485679 SCV003814570 uncertain significance Charcot-Marie-Tooth disease type 2A1 2019-05-21 criteria provided, single submitter clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV003153921 SCV003843068 uncertain significance Pheochromocytoma 2023-02-27 criteria provided, single submitter clinical testing The KIF1B c.5065A>G (p.Ser1689Gly) missense change has a maximum subpopulation frequency of 0.017% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with pheochromocytoma or neuroblastoma. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.

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