Submissions for variant NM_001130987.2(DYSF):c.5830C>T (p.Arg1944Ter)

gnomAD frequency: 0.00001  dbSNP: rs121908959

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000080312	SCV000335577	pathogenic	not provided	2015-09-22	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000080312	SCV000613217	pathogenic	not provided	2023-03-07	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). In multiple individuals with Miyoshi muscular dystrophy, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic. This variant is a common founder originating from Sueca, Spain (PMID: 16087766).
GeneDx	RCV000080312	SCV000680751	pathogenic	not provided	2023-03-24	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 16010686, 32400077, 33250842, 33215690, 30919934, 33715265, 31069529, 34559919, 33348118, 33610434, 20558759, 16087766)
Invitae	RCV000808564	SCV000948676	pathogenic	Qualitative or quantitative defects of dysferlin	2024-01-04	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg1905*) in the DYSF gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DYSF are known to be pathogenic (PMID: 17698709, 20301480). This variant is present in population databases (rs121908959, gnomAD 0.003%). This premature translational stop signal has been observed in individuals with dysferlinopathy (PMID: 16087766). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 6676). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity	RCV000080312	SCV002021876	pathogenic	not provided	2023-12-13	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003114177	SCV003800937	pathogenic	Autosomal recessive limb-girdle muscular dystrophy	2023-01-16	criteria provided, single submitter	clinical testing	Variant summary: DYSF c.5713C>T (p.Arg1905X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic within ClinVar (e.g. c.5938A>T [p.Lys1980Ter], c.5953_5956del [p.Gln1985fs]). The variant allele was found at a frequency of 1.2e-05 in 251484 control chromosomes (gnomAD). c.5713C>T has been reported in the literature as a biallelic genotype in multiple individuals affected with Limb-Girdle Muscular Dystrophy or Miyoshi Myopathy (e.g. Vilchez_2005, Park_2012, Ankala_2014, Izumi_2015). These data indicate that the variant is very likely to be associated with disease. Seven ClinVar submitters have assessed the variant since 2014: all have classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics	RCV000007061	SCV004194157	pathogenic	Miyoshi muscular dystrophy 1	2023-11-14	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000007063	SCV004808129	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2B	2024-03-29	criteria provided, single submitter	clinical testing
OMIM	RCV000007061	SCV000027257	pathogenic	Miyoshi muscular dystrophy 1	2005-08-01	no assertion criteria provided	literature only
OMIM	RCV000007062	SCV000027258	pathogenic	Distal myopathy with anterior tibial onset	2005-08-01	no assertion criteria provided	literature only
Counsyl	RCV000007063	SCV000788443	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2B	2017-04-21	no assertion criteria provided	clinical testing
OMIM	RCV000007063	SCV000809055	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2B	2005-08-01	no assertion criteria provided	literature only
GeneReviews	RCV000007061	SCV001981616	not provided	Miyoshi muscular dystrophy 1		no assertion provided	literature only	Founder variant in Spain
Natera, Inc.	RCV000007063	SCV002080337	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2B	2020-10-22	no assertion criteria provided	clinical testing