Submissions for variant NM_170707.4(LMNA):c.1583C>G (p.Thr528Arg)

dbSNP: rs57629361

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000057329	SCV000233096	pathogenic	not provided	2017-11-21	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000472329	SCV000548862	pathogenic	Charcot-Marie-Tooth disease type 2	2023-10-09	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 528 of the LMNA protein (p.Thr528Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant Emery-Dreifuss muscular dystrophy (PMID: 14684700, 20376791, 26165385). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 66850). 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 LMNA protein function. For these reasons, this variant has been classified as Pathogenic.
Genetic Services Laboratory, University of Chicago	RCV000499741	SCV000595633	likely pathogenic	Familial partial lipodystrophy, Dunnigan type	2013-02-08	criteria provided, single submitter	clinical testing
Kariminejad - Najmabadi Pathology & Genetics Center	RCV001814041	SCV001755599	pathogenic	Abnormality of the musculature	2021-07-10	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000057329	SCV002496940	pathogenic	not provided	2022-01-01	criteria provided, single submitter	clinical testing
Epithelial Biology; Institute of Medical Biology, Singapore	RCV000057329	SCV000088442	not provided	not provided		no assertion provided	not provided
GenomeConnect - Invitae Patient Insights Network	RCV003483458	SCV004228645	not provided	Congenital muscular dystrophy due to LMNA mutation		no assertion provided	phenotyping only	Variant interpreted as Pathogenic and reported on 12-04-2019 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.