Submissions for variant NM_001159699.2(FHL1):c.871G>A (p.Asp291Asn)

gnomAD frequency: 0.01175  dbSNP: rs151315725

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000228514	SCV000287134	benign	X-linked myopathy with postural muscle atrophy	2025-02-03	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000296313	SCV000336163	benign	not specified	2015-12-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000296313	SCV000522548	benign	not specified	2016-03-04	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Athena Diagnostics	RCV000991990	SCV001143923	benign	not provided	2018-08-24	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV003741168	SCV001157535	benign	Familial hemophagocytic lymphohistiocytosis type 1	2023-10-19	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000296313	SCV001623250	benign	not specified	2021-04-29	criteria provided, single submitter	clinical testing	Variant summary: FHL1 c.*51G>A is located in the untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of 0.011 in 183528 control chromosomes in the gnomAD database, including 17 homozygotes. The observed variant frequency is approximately 28 fold of the estimated maximal expected allele frequency for a pathogenic variant in FHL1 causing Emery-Dreifuss Muscular Dystrophy phenotype (0.00039), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.*51G>A in individuals affected with Emery-Dreifuss Muscular Dystrophy and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Ambry Genetics	RCV002408965	SCV002676150	benign	Cardiovascular phenotype	2019-01-03	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Breakthrough Genomics, Breakthrough Genomics	RCV000991990	SCV005279588	benign	not provided		criteria provided, single submitter	not provided
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000991990	SCV001800519	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000296313	SCV001921766	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000296313	SCV001930630	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000991990	SCV001952924	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000296313	SCV001965230	benign	not specified		no assertion criteria provided	clinical testing