ClinVar Miner

Submissions for variant NM_004260.4(RECQL4):c.1488C>G (p.Ile496Met)

gnomAD frequency: 0.00002  dbSNP: rs1358382637
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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 RCV000799018 SCV000938665 uncertain significance Baller-Gerold syndrome 2023-07-17 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with RECQL4-related conditions. This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 496 of the RECQL4 protein (p.Ile496Met). This variant is present in population databases (no rsID available, gnomAD 0.01%). ClinVar contains an entry for this variant (Variation ID: 645006). 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 RECQL4 protein function. 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.
Baylor Genetics RCV001292863 SCV001481544 uncertain significance Rothmund-Thomson syndrome type 2 2020-01-07 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx RCV002251518 SCV002521972 uncertain significance not provided 2022-05-25 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV004027977 SCV004939218 likely benign Inborn genetic diseases 2025-03-14 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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