ClinVar Miner

Submissions for variant NM_002907.4(RECQL):c.1465A>G (p.Ile489Val)

gnomAD frequency: 0.00014  dbSNP: rs146077019
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV003492142 SCV000838633 likely benign Hereditary cancer 2024-01-23 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001206987 SCV001378322 uncertain significance not provided 2024-01-27 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 489 of the RECQL protein (p.Ile489Val). This variant is present in population databases (rs146077019, gnomAD 0.05%). This missense change has been observed in individual(s) with breast cancer and/or pancreatic cancer (PMID: 19768149, 35264596). ClinVar contains an entry for this variant (Variation ID: 584806). 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 RECQL 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.
GeneDx RCV001206987 SCV001785780 uncertain significance not provided 2024-08-08 criteria provided, single submitter clinical testing Observed in individuals with breast cancer, leukemia, or pancreatic cancer (PMID: 19768149, 35264596, 35534704); In silico analysis indicates that this missense variant does not alter protein structure/function; Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (PMID: 25741868); This variant is associated with the following publications: (PMID: 35264596, 19768149, 35534704, 27248010, 19151156, 23396353)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001206987 SCV002046714 uncertain significance not provided 2023-04-25 criteria provided, single submitter clinical testing To the best of our knowledge, the variant has not been reported in individuals affected with RECQL-related diseases in the published literature, however, it has been reported in an individual affected with pancreatic cancer (PMID: 19768149 (2009)). 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.
Ambry Genetics RCV004026766 SCV002696313 likely benign not specified 2020-06-25 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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