Submissions for variant NM_032444.4(SLX4):c.5040G>C (p.Arg1680Ser)

dbSNP: rs199592185

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000630914	SCV000751887	uncertain significance	Fanconi anemia	2023-10-13	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 1680 of the SLX4 protein (p.Arg1680Ser). This variant is present in population databases (rs199592185, gnomAD 0.02%). 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: 526390). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Illumina Laboratory Services, Illumina	RCV001118089	SCV001276348	uncertain significance	Fanconi anemia complementation group P	2018-03-30	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV003237965	SCV002009290	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV001118089	SCV002790883	uncertain significance	Fanconi anemia complementation group P	2022-03-11	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003411491	SCV004108727	uncertain significance	SLX4-related disorder	2023-02-28	criteria provided, single submitter	clinical testing	The SLX4 c.5040G>C variant is predicted to result in the amino acid substitution p.Arg1680Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.017% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-3633211-C-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.