Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV001004981 | SCV001164524 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2B | 2018-12-03 | criteria provided, single submitter | research | The homozygous p.Phe1564SerfsTer17 variant in DYSF was identified by our study in one individual 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 1564 and leads to a premature termination codon 17 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 clinical significance of the p.Phe1564SerfsTer17 variant is likely pathogenic. ACMG/AMP Criteria applied: PM2, PVS1 (Richards 2015). |