ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.1819del (p.Val607fs) (rs1064796394)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000486027 SCV000573080 likely pathogenic not provided 2018-11-20 criteria provided, single submitter clinical testing Although the c.1819delG likely pathogenic variant in the LMNA gene has not been reported to our knowledge, this variant causes a shift in reading frame starting at codon valine 607, changing it to a tryptophan, and creating a premature stop codon at position 91 of the new reading frame, denoted p.Val607TrpfsX91. This likely pathogenic variant is predicted to result in replacement of the last 58 amino acid codons of the LMNA gene by 90 incorrect codons. Other downstream nonsense and frameshift variants have been reported in the Human Gene Mutation Database in association with cardiac disease, Hutchinson-Gilford progeria syndrome, and metabolic laminopathy (Stenson et al., 2014). Homozygous individuals have been described as more severely affected and functional studies suggest abnormal protein processing as the mechanism of disease (Cowan et al., 2010; Le Dour et al., 2011; Andre et al., 2015). Furthermore, the c.1819delG variant has not been observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). However, this variant lacks observation in a significant number of affected individuals, segregation data, and functional evidence, which would further clarify its pathogenicity.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.