The document summarizes a pathogenic missense mutation in the LMNA gene. The LMNA gene encodes lamin proteins that make up the nuclear lamina and mutations can cause several diseases. The specific mutation described creates a premature stop codon that is expected to result in an absent or disrupted lamin protein, consistent with known pathogenic loss-of-function variants in this gene.

1. NM_170707.4(LMNA):c.4G>T (p.Glu2Ter)
The nuclear lamina consists of a two-dimensional matrix of proteins located next to the inner nuclear membrane.
The lamin family of proteins make up the matrix and are highly conserved in evolution. During mitosis, the
lamina matrix is reversibly disassembled as the lamin proteins are phosphorylated. Lamin proteins are thought to
be involved in nuclear stability, chromatin structure and gene expression. Vertebrate lamins consist of two types, A
and B. Alternative splicing results in multiple transcript variants. Mutations in this gene lead to several diseases:
Emery-Dreifuss muscular dystrophy, familial partial lipodystrophy, limb girdle muscular dystrophy, dilated
cardiomyopathy, Charcot-Marie-Tooth disease, and Hutchinson-Gilford progeria syndrome.
Cytogenetic location: 1q22

2. This sequence change creates a premature translational stop signal (p.Glu2*) in the LMNA gene. It
is expected to result in an absent or disrupted protein product.While this variant is not present in
population databases, the frequency information is unreliable, as metrics indicate poor data quality
at this position in the ExAC database.This variant has not been reported in the literature in
individuals with LMNA-related disease. Loss-of-function variants in LMNA are known to be
pathogenic (PMID: 18585512, 18926329). For these reasons, this variant has been classified as
Pathogenic
DignosisticMutation: Miss sense Mutation