ClinVar Miner

Submissions for variant NM_001130987.2(DYSF):c.6096dup (p.Glu2033fs)

gnomAD frequency: 0.00005  dbSNP: rs398123799
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000080318 SCV000255775 pathogenic not provided 2020-06-24 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. 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.
Eurofins Ntd Llc (ga) RCV000080318 SCV000333039 pathogenic not provided 2015-07-14 criteria provided, single submitter clinical testing
GeneDx RCV000080318 SCV000568715 pathogenic not provided 2023-04-18 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect resulting in decreased or absent dysferlin expression (Gallardo et al., 2011); Frameshift 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; This variant is associated with the following publications: (PMID: 11053681, 30028523, 27447704, 32528171, 33715265, 22194990, 33610434, 35725460, 35741838, 27602406)
Invitae RCV000547387 SCV000649733 pathogenic Qualitative or quantitative defects of dysferlin 2024-01-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu1994Argfs*3) 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 (rs780234359, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with limb-girdle muscular dystrophy type 2B and Miyoshi myopathy (PMID: 11053681, 16010686, 16100712, 17070050, 17698709, 18853459, 19528035, 22194990, 26404900, 27447704, 27602406, 27858744). ClinVar contains an entry for this variant (Variation ID: 94351). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV000080318 SCV002021866 pathogenic not provided 2023-08-23 criteria provided, single submitter clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV002243709 SCV002512431 pathogenic Miyoshi muscular dystrophy 1; Autosomal recessive limb-girdle muscular dystrophy type 2B; Distal myopathy with anterior tibial onset 2021-12-28 criteria provided, single submitter clinical testing ACMG classification criteria: PVS1 very strong, PS4 strong, PM2 moderate, PM3 strong
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV000179122 SCV002769386 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2B 2020-10-19 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.3, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with dysferlinenopathy. (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0115 - Variants in this gene are known to have variable expressivity. Patients with the same genotype have been reported with different forms of myopathy, with no distinct genotype-phenotype correlation (OMIM, PMID: 27602406). 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (14 heterozygotes, 0 homozygotes). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. Patients with biallelic NMD-predicted variants have been reported in many patients with dysferlinenopathy (PMID: 27602406, Decipher, ClinVar). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported in multiple homozygous and compound heterozygous patients with dysferlinenopathies (ClinVar, PMID: 27602406). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Baylor Genetics RCV003466989 SCV004194208 pathogenic Miyoshi muscular dystrophy 1 2023-09-19 criteria provided, single submitter clinical testing
Counsyl RCV000179122 SCV001132385 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2B 2017-01-06 no assertion criteria provided clinical testing
Natera, Inc. RCV000179122 SCV001457858 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2B 2020-09-16 no assertion criteria provided clinical testing

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