Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
RCV001754577 | SCV001994830 | likely pathogenic | Hutchinson-Gilford syndrome | 2021-11-01 | criteria provided, single submitter | clinical testing | The variant c.164A>G (p.(Glu55Gly)) in exon 1 of the LMNA gene is not found in the gnomAD database, it affects a moderately conserved nucleotide, a highly conserved amino acid within a protein domain and is located within a mutational hot spot and there is a moderate physicochemical difference between Glu and Gly. This variant has a pathogenic computational verdict based on 11 pathogenic predictions from BayesDel_addAF, DANN, DEOGEN2, EIGEN, FATHMM-MKL, LIST-S2, M-CAP, MVP, MutationAssessor, MutationTaster and SIFT vs 1 benign prediction from PrimateAI. The variant has been described in the literature to be causative for an aggressive atypical neonatal form of progeria without progerin accumulation. Functional in vitro analysis showed a damaging effect on protein function (PMID: 27334370). ACMG criteria used for classification: PM1, PM2, PP2, PP3, PP4, PS3_supp, PP5. |