Submissions for variant NM_004425.4(ECM1):c.1246C>T (p.Arg416Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Neuberg Centre For Genomic Medicine, NCGM	RCV003337853	SCV004048216	likely pathogenic	Lipid proteinosis		criteria provided, single submitter	clinical testing	The c.1327C>T(p.Arg443Ter) variant in ECM1 has been reported previously in homozygous state in individual affected with lipoid proteinosis (Srinivas, Sahana M., et al.). The p.Arg443Ter variant is reported with the allele frequency of 003189% in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic.
Medical Genetics Laboratory, Etlik City Hospital	RCV003337853	SCV004801903	pathogenic	Lipid proteinosis	2024-03-25	criteria provided, single submitter	clinical testing	The c.1246C>T (p.Arg416*) variant located on Exon 8/10 of the ECM1 gene and resulting in a premature stop codon was identified in the proband in the homozygous state. Both unaffected parents were confirmed as heterozygous carriers through Sanger sequencing. The sequencing analysis of the ECM1 gene in two siblings of the proband showed normal results. This variant was absent in population databases, including Turkish Variome, ExAC, and gnomAD. According to the ACMG interpretation standards, c.1246C>T was classified as a pathogenic variant (PVS1, PM2, PP1, PP4).