ClinVar Miner

Submissions for variant NM_003494.3(DYSF):c.2779del (p.Ala927Leufs)

dbSNP: rs727503909
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 12
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000599552 SCV000228343 pathogenic not provided 2016-11-09 criteria provided, single submitter clinical testing
Invitae RCV000546602 SCV000649638 pathogenic Qualitative or quantitative defects of dysferlin 2023-12-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ala927Leufs*21) 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 (rs745407251, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with limb-girdle muscular dystrophy type 2B (LGMD2B), Miyoshi myopathy or pseudometabolic muscular dystrophy (PMID: 16010686, 17825554, 18832576, 18853459, 19084402, 22194990, 25821721). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 6685). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000599552 SCV000709975 pathogenic not provided 2017-12-28 criteria provided, single submitter clinical testing The c.2779delG pathogenic variant in the DYSF gene has been previously reported multiple times in association with DYSF-related disorders when present in the homozygous state or when in trans with another pathogenic DYSF variant (Krahn et al., 2009; Paradas et al., 2009; Ceyhan-Birsoy et al., 2015). This variant is observed in 7/34,416 (0.02%) alleles from individuals of Latino background (Lek et al., 2016). The c.2779delG variant causes a frameshift starting with codon Alanine 927, changes this amino acid to a Leucine residue, and creates a premature Stop codon at position 21 of the new reading frame, denoted p.Ala927LeufsX21. This variant is predicted to cause loss of normal protein function either through protein truncation of nonsense-mediated mRNA decay.
Athena Diagnostics RCV000599552 SCV001477220 pathogenic not provided 2020-08-31 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). This variant has been identified in multiple unrelated individuals with clinical features associated with this gene (PMID:25821721, 22194990, 19084402, 16010686, 18853459, 17825554). In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic.
Revvity Omics, Revvity RCV000599552 SCV002021826 pathogenic not provided 2023-06-19 criteria provided, single submitter clinical testing
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV000311139 SCV002764676 pathogenic Miyoshi muscular dystrophy 1 2021-05-06 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000599552 SCV003916115 pathogenic not provided 2023-02-01 criteria provided, single submitter clinical testing DYSF: PVS1, PM2, PM3, PS4:Supporting
Baylor Genetics RCV000311139 SCV004194187 pathogenic Miyoshi muscular dystrophy 1 2024-02-24 criteria provided, single submitter clinical testing
OMIM RCV000007072 SCV000027268 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2B 2009-01-01 no assertion criteria provided literature only
Genetic Diseases Diagnostic Center, Koc University Hospital RCV000311139 SCV000864397 likely pathogenic Miyoshi muscular dystrophy 1 2018-12-18 no assertion criteria provided clinical testing
Natera, Inc. RCV000007072 SCV001458660 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2B 2020-09-16 no assertion criteria provided clinical testing
GeneReviews RCV000311139 SCV001981612 not provided Miyoshi muscular dystrophy 1 no assertion provided literature only Founder variant in Jews of the Caucasus

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.