Submissions for variant NM_001130987.2(DYSF):c.5757del (p.Glu1920fs)

dbSNP: rs1573100371

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Tan Tock Seng Hospital, National Healthcare Group	RCV000850237	SCV000987702	pathogenic	Miyoshi muscular dystrophy 1		criteria provided, single submitter	clinical testing	This single base pair deletion in exon 51 of DYSF gene results in a frameshift and premature truncation of the protein (p.Glu1920SerfsTer85). This is expected to result in disrupted or non-functional protein. It is not present in population databases (GnomAD genomes) and is predicted to be damaging by MutationTaster2. This variant has not been reported in the literature in individuals with DYSF-related disease. Loss-of-function variants in DYSF are known to be pathogenic (PMID: 17698709, 20301480). For these reasons, this variant has been classified as Pathogenic.
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine	RCV003338828	SCV004047643	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2B		criteria provided, single submitter	clinical testing	The frameshift c.5757del (p.Glu1920SerfsTer85) variant has been submitted to ClinVar as Pathogenic. The p.Glu1920SerfsTer85 variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant causes a frameshift starting with codon Glutamic Acid 1920, changes this amino acid to Serine residue, and creates a premature Stop codon at position 85 of the new reading frame, denoted p.Glu1920SerfsTer85. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic.