Submissions for variant NM_001130987.2(DYSF):c.3946A>G (p.Ile1316Val)

gnomAD frequency: 0.00491  dbSNP: rs121908954

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000153183	SCV000309678	likely benign	not specified		criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000153183	SCV000332041	benign	not specified	2015-07-09	criteria provided, single submitter	clinical testing
GeneDx	RCV000658868	SCV000512918	benign	not provided	2020-04-10	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24123366, 25898921, 9731526, 25525159, 11468312, 21816046, 22995991, 16934466, 20544924, 30919934, 32528171)
Athena Diagnostics	RCV000658868	SCV000613205	benign	not provided	2018-09-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000509353	SCV000649673	benign	Qualitative or quantitative defects of dysferlin	2024-01-31	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000658868	SCV000780667	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	DYSF: BP4, BS2
Mendelics	RCV000681611	SCV001135888	likely benign	Autosomal recessive limb-girdle muscular dystrophy type 2B	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV004547461	SCV001297889	uncertain significance	DYSF-related disorder	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Genome-Nilou Lab	RCV000007049	SCV001786956	uncertain significance	Miyoshi muscular dystrophy 1	2021-07-14	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000681611	SCV001786957	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2B	2021-07-14	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001563901	SCV001786958	uncertain significance	Distal myopathy with anterior tibial onset	2021-07-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000153183	SCV002103695	likely benign	not specified	2022-02-18	criteria provided, single submitter	clinical testing	Variant summary: DYSF c.3892A>G (p.Ile1298Val) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0046 in 248942 control chromosomes, predominantly at a frequency of 0.0072 within the Non-Finnish European subpopulation in the gnomAD database, including 6 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 2.35 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 a benign polymorphism found primarily in populations of Non-Finnish European origin. c.3892A>G has been reported in the literature in individuals affected with Limb-Girdle Muscular Dystrophy, Autosomal Recessive (examples: Liu_1998, ten Dam_2019). These reports do not provide unequivocal conclusions about association of the variant with Limb-Girdle Muscular Dystrophy, Autosomal Recessive. Nine clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments: seven classified as likely benign/benign while two classified as VUS. Based on the evidence outlined above, the variant was classified as likely benign.
OMIM	RCV000007049	SCV000027245	pathogenic	Miyoshi muscular dystrophy 1	1998-09-01	no assertion criteria provided	literature only
GenomeConnect, ClinGen	RCV000509353	SCV000606886	not provided	Qualitative or quantitative defects of dysferlin		no assertion provided	phenotyping only	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
OMIM	RCV000681611	SCV000809051	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2B	1998-09-01	no assertion criteria provided	literature only
Natera, Inc.	RCV000681611	SCV001455234	benign	Autosomal recessive limb-girdle muscular dystrophy type 2B	2020-01-10	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000658868	SCV002034040	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000658868	SCV002036696	likely benign	not provided		no assertion criteria provided	clinical testing