Submissions for variant NM_001130987.2(DYSF):c.4179del (p.Lys1394fs)

dbSNP: rs1574340607

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Belal Azab Laboratory, The University of Jordan	RCV000993848	SCV000930007	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2B	2019-07-01	criteria provided, single submitter	research
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV000993848	SCV001164516	likely pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2B	2018-12-03	criteria provided, single submitter	research	The homozygous p.Lys1394ArgfsTer14 variant in DYSF was identified by our study in two unrelated individuals with limb-girdle muscular dystrophy (LGMD). This variant was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at position 1394 and leads to a premature termination codon 14 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the DYSF gene is an established disease mechanism in autosomal recessive LGMD, and this is a loss of function variant. In summary, although additional studies are required to fully establish its clinical significance, the p.Lys1394ArgfsTer14 variant is likely pathogenic. ACMG/AMP Criteria applied: PM2, PVS1 (Richards 2015).