Submissions for variant NM_032444.4(SLX4):c.4057C>A (p.His1353Asn)

dbSNP: rs142205392

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000232675	SCV000291085	likely benign	Fanconi anemia	2023-12-23	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001094330	SCV000396833	uncertain significance	Fanconi anemia complementation group P	2018-01-13	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.
Baylor Genetics	RCV001094330	SCV001482658	uncertain significance	Fanconi anemia complementation group P	2019-04-03	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
St. Jude Molecular Pathology, St. Jude Children's Research Hospital	RCV001094330	SCV001775516	uncertain significance	Fanconi anemia complementation group P	2021-03-17	criteria provided, single submitter	clinical testing
GeneDx	RCV001556641	SCV001778256	uncertain significance	not provided	2021-05-06	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with breast or ovarian cancer (Sha 2013, Song 2020); This variant is associated with the following publications: (PMID: 23840564, 32546565)
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV001556641	SCV002010068	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV001820768	SCV002066167	uncertain significance	not specified	2021-09-01	criteria provided, single submitter	clinical testing	DNA sequence analysis of the SLX4 gene demonstrated a sequence change, c.4057C>A, in exon 12 that results in an amino acid change, p.His1353Asn. 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 0.07% in European populations (dbSNP rs142205392). The p.His1353Asn change affects a poorly conserved amino acid residue located in a domain of the SLX4 protein that is not known to be functional. The p.His1353Asn substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to the lack of functional studies, the clinical significance of the p.His1353Asn change remains unknown at this time.
Sema4, Sema4	RCV000232675	SCV002529340	uncertain significance	Fanconi anemia	2021-10-04	criteria provided, single submitter	curation