Submissions for variant NM_170707.4(LMNA):c.1007G>A (p.Arg336Gln)

gnomAD frequency: 0.00003  dbSNP: rs58105277

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000225878	SCV000291541	pathogenic	Charcot-Marie-Tooth disease type 2	2023-04-06	criteria provided, single submitter	clinical testing	This variant is present in population databases (rs58105277, gnomAD 0.01%). For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 66758). This missense change has been observed in individuals with Emery-Dreifuss muscular dystrophy and dilated cardiomyopathy (PMID: 29693488). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 336 of the LMNA protein (p.Arg336Gln).
Ambry Genetics	RCV002426615	SCV002728887	uncertain significance	Cardiovascular phenotype	2020-09-14	criteria provided, single submitter	clinical testing	The p.R336Q variant (also known as c.1007G>A), located in coding exon 6 of the LMNA gene, results from a G to A substitution at nucleotide position 1007. The arginine at codon 336 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been detected in multiple patients with Emery-Dreifuss muscular dystrophy, but was also detected in several unaffected individuals (Raffaele Di Barletta M et al. Am. J. Hum. Genet., 2000 Apr;66:1407-12; Sanna T et al. Eur. Heart J., 2003 Dec;24:2227-36; Peretto G et al. Ann. Intern. Med., 2019 10;171:458-463; Bernasconi P et al. Nucleus, 2018 01;9:292-304; Park J et al. Genet. Med., 2020 01;22:102-111). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Athena Diagnostics Inc	RCV000057214	SCV002771304	uncertain significance	not provided	2021-12-21	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002483086	SCV002803245	uncertain significance	Dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome; Dilated cardiomyopathy 1A; Charcot-Marie-Tooth disease type 2B1; Emery-Dreifuss muscular dystrophy 2, autosomal dominant; Heart-hand syndrome, Slovenian type; Hutchinson-Gilford syndrome; Familial partial lipodystrophy, Dunnigan type; Mandibuloacral dysplasia with type A lipodystrophy; Congenital muscular dystrophy due to LMNA mutation; Emery-Dreifuss muscular dystrophy 3, autosomal recessive; Restrictive dermopathy 2	2021-11-02	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000057214	SCV004698994	uncertain significance	not provided	2023-12-01	criteria provided, single submitter	clinical testing	LMNA: PM1, PS4:Supporting
Epithelial Biology; Institute of Medical Biology, Singapore	RCV000057214	SCV000088327	not provided	not provided		no assertion provided	not provided