ClinVar Miner

Submissions for variant NM_205836.3(FBXO38):c.1834G>A (p.Val612Ile)

gnomAD frequency: 0.00007  dbSNP: rs201999494
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002232385 SCV000653618 uncertain significance Distal hereditary motor neuropathy type 2 2023-11-17 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 612 of the FBXO38 protein (p.Val612Ile). This variant is present in population databases (rs201999494, gnomAD 0.02%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with FBXO38-related conditions. ClinVar contains an entry for this variant (Variation ID: 473949). 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 FBXO38 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.
Ambry Genetics RCV004024255 SCV002714679 likely benign not specified 2019-10-01 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.
Breakthrough Genomics, Breakthrough Genomics RCV004691900 SCV005188663 uncertain significance not provided criteria provided, single submitter not provided

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