ClinVar Miner

Submissions for variant NM_032444.4(SLX4):c.2210G>A (p.Arg737His)

gnomAD frequency: 0.00029  dbSNP: rs146901714
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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 RCV000459845 SCV000547452 uncertain significance Fanconi anemia 2022-06-20 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 737 of the SLX4 protein (p.Arg737His). This variant is present in population databases (rs146901714, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with SLX4-related conditions. ClinVar contains an entry for this variant (Variation ID: 407912). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 RCV001764400 SCV002009045 uncertain significance not provided 2019-08-16 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Genetic Services Laboratory, University of Chicago RCV001821255 SCV002069517 uncertain significance not specified 2019-12-17 criteria provided, single submitter clinical testing DNA sequence analysis of the SLX4 gene demonstrated a sequence change, c.2210G>A, in exon 11 that results in an amino acid change, p.Arg737His. This sequence change does not appear to have been previously described in patients with SLX4-related disorders and has been described in the gnomAD database with a frequency of 0.08% in African populations (dbSNP rs146901714). The p.Arg737His change affects a highly conserved amino acid residue located in a domain of the SLX4 protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Arg737His substitution. Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Arg737His change remains unknown at this time.

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