Submissions for variant NM_018062.4(FANCL):c.238C>G (p.Leu80Val)

gnomAD frequency: 0.00008  dbSNP: rs563513081

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000467748	SCV000547811	uncertain significance	Fanconi anemia	2022-10-26	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 80 of the FANCL protein (p.Leu80Val). This variant is present in population databases (rs563513081, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with FANCL-related conditions. ClinVar contains an entry for this variant (Variation ID: 408230). 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 not expected to disrupt FANCL 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	RCV001137463	SCV001297404	uncertain significance	Fanconi anemia complementation group L	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.
Baylor Genetics	RCV001137463	SCV002030146	uncertain significance	Fanconi anemia complementation group L	2021-07-27	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Genetic Services Laboratory, University of Chicago	RCV001821269	SCV002067127	uncertain significance	not specified	2019-12-11	criteria provided, single submitter	clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV002252132	SCV002522874	uncertain significance	See cases	2021-10-18	criteria provided, single submitter	clinical testing	ACMG classification criteria: PM2, BP4
Sema4, Sema4	RCV000467748	SCV002527278	uncertain significance	Fanconi anemia	2022-02-15	criteria provided, single submitter	curation
Fulgent Genetics, Fulgent Genetics	RCV001137463	SCV002804983	uncertain significance	Fanconi anemia complementation group L	2022-04-15	criteria provided, single submitter	clinical testing