ClinVar Miner

Submissions for variant NM_003494.3(DYSF):c.2779del (p.Ala927Leufs) (rs727503909)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000599552 SCV000228343 pathogenic not provided 2016-11-09 criteria provided, single submitter clinical testing
Invitae RCV000546602 SCV000649638 pathogenic Qualitative or quantitative defects of dysferlin 2019-12-11 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. This variant is present in population databases (rs745407251, ExAC 0.02%). This variant has been reported in the literature in multiple individuals affected with limb-girdle muscular dystrophy type 2B (LGMD2B), Miyoshi myopathy or pseudometabolic muscular dystrophy (PMID: 16010686, 25821721, 22194990, 18853459, 17825554, 19084402, 18832576). In all affected individuals, this variant was reported in the homozygous or compound heterozygous state. In several families, this variant was reported to co-segregate with disease (PMID: 19084402, 25821721). ClinVar contains an entry for this variant (Variation ID: 6685). Loss-of-function variants in DYSF are known to be pathogenic (PMID: 17698709, 20301480). 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.
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

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