Submissions for variant NM_170707.4(LMNA):c.134A>G (p.Tyr45Cys)

dbSNP: rs58436778

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000692072	SCV000819879	pathogenic	Charcot-Marie-Tooth disease type 2	2023-10-04	criteria provided, single submitter	clinical testing	This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 45 of the LMNA protein (p.Tyr45Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant laminopathies (PMID: 10939567, 20848652, 23183350; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 66807). 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. Experimental studies have shown that this missense change affects LMNA function (PMID: 31434876). For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV002468560	SCV002764778	likely pathogenic	Emery-Dreifuss muscular dystrophy 2, autosomal dominant	2021-03-15	criteria provided, single submitter	clinical testing
Epithelial Biology; Institute of Medical Biology, Singapore	RCV000057272	SCV000088385	not provided	not provided		no assertion provided	not provided
Eurofins Ntd Llc (ga)	RCV000057272	SCV000113212	uncertain significance	not provided	2016-02-09	flagged submission	clinical testing