Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
EGL Genetic 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. |
Gene |
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 Inc | RCV000599552 | SCV001477220 | pathogenic | not provided | 2020-08-31 | criteria provided, single submitter | clinical testing | The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and found in general population data at a frequency that is consistent with pathogenicity. |
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, |
RCV000311139 | SCV000864397 | likely pathogenic | Miyoshi muscular dystrophy 1 | 2018-12-18 | no assertion criteria provided | clinical testing | |
Natera, |
RCV000007072 | SCV001458660 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2B | 2020-09-16 | no assertion criteria provided | clinical testing |