Submissions for variant NM_001130987.2(DYSF):c.1914C>T (p.Tyr638=)

gnomAD frequency: 0.03282  dbSNP: rs35721373

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Limb Girdle Muscular Dystrophy Variant Curation Expert Panel, ClinGen	RCV004998209	SCV005620328	benign	Autosomal recessive limb-girdle muscular dystrophy	2025-01-08	reviewed by expert panel	curation	The NM_003494.4: c.1860C>T (p.Tyr620=) variant in DYSF, which is also known as NM_001130987.2: c.1914C>T (p.Tyr638=), is a synonymous (silent) variant that is not located in a splice region (outside of the first and the last 3 bases of the exon). The filtering allele frequency is 0.05612 for South Asian exome chromosomes in gnomAD v2.1.1 (the lower threshold of the 95% CI of 1787/30616), which is higher than the VCEP threshold of 0.003 (BA1). The SpliceAI prediction score for this variant is 0.08, which is greater than the VCEP threshold of <0.05 (BP4 and BP7 not applied). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive limb girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen LGMD VCEP (LGMD VCEP specifications version 1.0.0; 01/08/2025): BA1.
Eurofins Ntd Llc (ga)	RCV000080245	SCV000112140	benign	not specified	2012-08-15	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000080245	SCV000269049	benign	not specified	2015-01-13	criteria provided, single submitter	clinical testing	p.Tyr638Tyr in exon 20 of DYSF: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 4.7% (209/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs35721373).
PreventionGenetics, part of Exact Sciences	RCV000080245	SCV000309650	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000262188	SCV000431739	likely benign	Miyoshi myopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000317599	SCV000431740	likely benign	Limb-girdle muscular dystrophy, recessive	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000080245	SCV000522679	benign	not specified	2016-02-11	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000541345	SCV000649615	benign	Qualitative or quantitative defects of dysferlin	2025-02-03	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000541345	SCV001297638	likely benign	Qualitative or quantitative defects of dysferlin	2018-01-12	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Genome-Nilou Lab	RCV001527213	SCV001738159	benign	Miyoshi muscular dystrophy 1	2021-06-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001274449	SCV001875864	benign	Autosomal recessive limb-girdle muscular dystrophy type 2B	2021-07-30	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001664338	SCV001876191	benign	Distal myopathy with anterior tibial onset	2021-07-30	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001795099	SCV005257053	likely benign	not provided		criteria provided, single submitter	not provided
Genetic Services Laboratory, University of Chicago	RCV000080245	SCV000151017	likely benign	not specified		no assertion criteria provided	clinical testing	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.
Natera, Inc.	RCV001274449	SCV001458650	benign	Autosomal recessive limb-girdle muscular dystrophy type 2B	2020-09-16	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000080245	SCV002034623	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001795099	SCV002035861	likely benign	not provided		no assertion criteria provided	clinical testing