Submissions for variant NM_002296.4(LBR):c.1174G>A (p.Gly392Arg)

dbSNP: rs1236962991

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002527448	SCV003459846	likely pathogenic	not provided	2022-08-22	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 392 of the LBR protein (p.Gly392Arg). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of autosomal recessive LBR-related conditions (PMID: 29068549). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 446676). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt LBR protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Dan Cohn Lab, University Of California Los Angeles	RCV000515924	SCV000612103	pathogenic	Jeune thoracic dystrophy	2017-06-01	no assertion criteria provided	research
University of Washington Center for Mendelian Genomics, University of Washington	RCV000515924	SCV001479762	likely pathogenic	Jeune thoracic dystrophy		no assertion criteria provided	research