Submissions for variant NM_021922.3(FANCE):c.1018G>C (p.Gly340Arg)

gnomAD frequency: 0.00032  dbSNP: rs45524646

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000231935	SCV000290604	uncertain significance	Fanconi anemia complementation group E	2022-10-31	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 340 of the FANCE protein (p.Gly340Arg). This variant is present in population databases (rs45524646, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with FANCE-related conditions. ClinVar contains an entry for this variant (Variation ID: 134340). 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 expected to disrupt FANCE 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.
Illumina Laboratory Services, Illumina	RCV000231935	SCV000462669	uncertain significance	Fanconi anemia complementation group E	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.
Fulgent Genetics, Fulgent Genetics	RCV000231935	SCV000895764	uncertain significance	Fanconi anemia complementation group E	2022-02-09	criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV001194808	SCV002011427	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
GeneDx	RCV001194808	SCV005327701	uncertain significance	not provided	2023-12-24	criteria provided, single submitter	clinical testing	Reported in a patient with severe aplastic anemia referred for whole exome sequencing (PMID: 35776903); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 24728327, 35776903)
ITMI	RCV000121014	SCV000085182	not provided	not specified	2013-09-19	no assertion provided	reference population
Leiden Open Variation Database	RCV001194808	SCV001364605	uncertain significance	not provided	2011-02-07	no assertion criteria provided	curation	Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach.