ClinVar Miner

Submissions for variant NM_032444.4(SLX4):c.3676C>T (p.Arg1226Trp)

gnomAD frequency: 0.00114  dbSNP: rs142008398
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000552069 SCV000626424 benign Fanconi anemia 2023-12-11 criteria provided, single submitter clinical testing
Baylor Genetics RCV001293953 SCV001482657 uncertain significance Fanconi anemia complementation group P 2019-11-13 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx RCV001572565 SCV001797228 uncertain significance not provided 2021-05-25 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function
Sema4, Sema4 RCV000552069 SCV002529329 uncertain significance Fanconi anemia 2021-10-18 criteria provided, single submitter curation
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV001293953 SCV004015509 likely benign Fanconi anemia complementation group P 2023-07-07 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003960260 SCV004781807 likely benign SLX4-related disorder 2022-02-18 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Genetic Services Laboratory, University of Chicago RCV003151083 SCV003840065 uncertain significance not specified 2022-09-08 no assertion criteria provided clinical testing DNA sequence analysis of the SLX4 gene demonstrated a sequence change, c.3676C>T, in exon 12 that results in an amino acid change, p.Arg1226Trp. This sequence change has been previously described in familial breast cancer cases (PMID: 23840564). This sequence change has been described in the gnomAD database with a frequency of 0.4% in the African/African American subpopulation (dbSNP rs142008398). The p.Arg1226Trp change affects a poorly conserved amino acid residue located in a domain of the SLX4 protein that is not known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Arg1226Trp substitution. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Arg1226Trp change remains unknown at this time.

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