Submissions for variant NM_001130987.2(DYSF):c.5815_5816del (p.Ser1939fs)

dbSNP: rs398123796

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000305675	SCV000333460	pathogenic	not provided	2015-07-28	criteria provided, single submitter	clinical testing
Invitae	RCV000703813	SCV000832732	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.Ser1900Glnfs*14) 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 (rs778260292, gnomAD 0.008%). This premature translational stop signal has been observed in individuals with Miyoshi myopathy (PMID: 9731526, 18853459, 19528035, 19594366, 23530687). This variant is also known as 6071,2delAG. ClinVar contains an entry for this variant (Variation ID: 94344). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV000305675	SCV001168603	pathogenic	not provided	2018-12-12	criteria provided, single submitter	clinical testing	The c.5698_5699delAG pathogenic variant in the DYSF gene has been reported previously in multiple unrelated individuals with dysferlinopathy who had a second DYSF variant identified (Takahashi et al., 2003; Klinge et al., 2010; Ankala et al., 2014). Due to use of alternative nomenclature, this variant has also been reported as c.6071_6072delAG (Takahashi et al., 2003). The deletion causes a frameshift starting with codon Serine 1900, changes this amino acid to a Glutamine residue and creates a premature Stop codon at position 14 of the new reading frame, denoted p.Ser1900GlnfsX14. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.5698_5699delAG variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016)
CeGaT Center for Human Genetics Tuebingen	RCV000305675	SCV001247524	pathogenic	not provided	2018-06-01	criteria provided, single submitter	clinical testing
Kids Neuroscience Centre, Sydney Children's Hospitals Network	RCV001274109	SCV001571525	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2B		criteria provided, single submitter	provider interpretation	The c.5698_5699del variant creates a frameshift and premature termination codon (p.(Ser1900Glnfs*14)). These transcripts are predicted to be degraded by nonsense mediated decay (NMD). Any mis -spliced DYSF transcripts that escape NMD encode DYSF protein lacking 181 amino acids from the C-terminus, including 42 amino acids from the C2 calcium dependant membrane targeting domain and the entire transmembrane domain.
Revvity Omics, Revvity	RCV000305675	SCV002021867	pathogenic	not provided	2023-06-06	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003460753	SCV004196519	pathogenic	Miyoshi muscular dystrophy 1	2023-05-29	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000305675	SCV004229611	pathogenic	not provided	2023-03-22	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 individuals with limb-girdle muscular dystrophy or Miyoshi muscular dystrophy. 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.
Natera, Inc.	RCV001274109	SCV001457855	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2B	2020-09-16	no assertion criteria provided	clinical testing