Submissions for variant NM_004006.3(DMD):c.2366A>G (p.Glu789Gly)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Neuberg Centre For Genomic Medicine, NCGM	RCV005208306	SCV005849283	uncertain significance	Becker muscular dystrophy	2023-06-22	criteria provided, single submitter	clinical testing	The observed missense c.2366A>G (p.Glu789Gly) variant in DMD gene has not been previously reported as a pathogenic nor as a benign variant, to our knowledge. The p.Glu789Gly variant is absent in gnomAD exomes. This variant has not been submitted to the ClinVar database. Multiple lines of computational evidences (Polyphen - Pobably damaging, SIFT- Damaging, MutationTaster - Disease causing) predict a damaging effect on protein structure and function for this variant. The reference amino acid of p.Glu789Gly in DMD gene is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Glu at position 789 is changed to a Gly changing protein sequence and it might alter its composition and physico-chemical properties. Another missense variant c.2365G>A (p.Glu789Lys) in the same position of this gene has previously been reported to be disease causing (Alcántara-Ortigoza MA, et al., 2019), suggesting that this residue might be of clinical significance. For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS).