ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.4105G>A (p.Val1369Met)

dbSNP: rs201225325
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001317973 SCV001508656 uncertain significance Fanconi anemia 2025-01-22 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1369 of the FANCA protein (p.Val1369Met). This variant is present in population databases (rs201225325, gnomAD 0.006%). This missense change has been observed in individual(s) with FANCA-related conditions (PMID: 26580448, 28767289). ClinVar contains an entry for this variant (Variation ID: 1018645). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt FANCA protein function with a negative predictive value of 95%. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003478776 SCV004218602 uncertain significance not provided 2023-07-07 criteria provided, single submitter clinical testing In the published literature, this variant has been reported in individuals affected with a high grade glioma (PMID: 26580448 (2015)) and pancreatic neuroendocrine tumor (PMID: 28767289 (2017)). The frequency of this variant in the general population, 0.000008 (2/250990 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Mayo Clinic Laboratories, Mayo Clinic RCV003478776 SCV004224276 uncertain significance not provided 2022-12-13 criteria provided, single submitter clinical testing
Natera, Inc. RCV001317973 SCV002092477 uncertain significance Fanconi anemia 2020-01-20 no assertion criteria provided clinical testing

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