Submissions for variant NM_001130987.2(DYSF):c.386G>A (p.Gly129Glu)

gnomAD frequency: 0.00411  dbSNP: rs34997054

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000210633	SCV000262981	benign	Inborn genetic diseases	2013-11-14	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: 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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000080277	SCV000269053	benign	not specified	2016-03-03	criteria provided, single submitter	clinical testing	p.Gly129Glu in exon 5 of DYSF: This variant is not expected to have clinical sig nificance because it has been identified in 1.8% (162/8872) of European chromoso mes, including 3 homozygotes by the Exome Aggregation Consortium (ExAC, http://e xac.broadinstitute.org; dbSNP rs34997054).
Eurofins Ntd Llc (ga)	RCV000080277	SCV000331938	benign	not specified	2015-07-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000080277	SCV000519409	benign	not specified	2016-09-05	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.
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000499917	SCV000588370	likely pathogenic	Muscular dystrophy	2017-06-18	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000527027	SCV000649671	benign	Qualitative or quantitative defects of dysferlin	2025-01-30	criteria provided, single submitter	clinical testing
Counsyl	RCV000675166	SCV000800786	likely benign	Autosomal recessive limb-girdle muscular dystrophy type 2B	2017-09-12	criteria provided, single submitter	clinical testing
Mendelics	RCV000675166	SCV001135886	benign	Autosomal recessive limb-girdle muscular dystrophy type 2B	2019-05-28	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001449935	SCV001653368	likely benign	Miyoshi muscular dystrophy 1	2021-05-18	criteria provided, single submitter	clinical testing
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	RCV000675166	SCV001984272	benign	Autosomal recessive limb-girdle muscular dystrophy type 2B	2020-01-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000080277	SCV002103698	benign	not specified	2022-02-22	criteria provided, single submitter	clinical testing	Variant summary: DYSF c.383G>A (p.Gly128Glu) results in a non-conservative amino acid change located in the Ferlin, first C2 domain (IPR037726) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0071 in 156748 control chromosomes in the gnomAD database, including 21 homozygotes. The observed variant frequency is approximately 2-fold of the estimated maximal expected allele frequency for a pathogenic variant in DYSF causing Limb-Girdle Muscular Dystrophy, Autosomal Recessive phenotype (0.0031), strongly suggesting that the variant is benign. Eleven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and reported the variant with conflicting assessments (benign/likely benign [n=8], uncertain significance [n=2], likely pathogenic [n=1]). Based on the evidence outlined above, the variant was classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV001573049	SCV004154961	benign	not provided	2025-01-01	criteria provided, single submitter	clinical testing	DYSF: BS1, BS2
Molecular Genetics, Royal Melbourne Hospital	RCV003993796	SCV004812268	likely benign	Autosomal recessive limb-girdle muscular dystrophy	2024-02-05	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003891555	SCV000309677	benign	DYSF-related disorder	2019-12-16	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Natera, Inc.	RCV000675166	SCV001457598	benign	Autosomal recessive limb-girdle muscular dystrophy type 2B	2020-09-16	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001573049	SCV001798353	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001573049	SCV001931154	likely benign	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000080277	SCV001962808	benign	not specified		no assertion criteria provided	clinical testing