Submissions for variant NM_170707.4(LMNA):c.71C>T (p.Thr24Ile)

gnomAD frequency: 0.00001  dbSNP: rs1195524446

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Fulgent Genetics, Fulgent Genetics	RCV002495854	SCV002793838	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	2022-04-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003284369	SCV004009215	uncertain significance	Cardiovascular phenotype	2023-04-06	criteria provided, single submitter	clinical testing	The p.T24I variant (also known as c.71C>T), located in coding exon 1 of the LMNA gene, results from a C to T substitution at nucleotide position 71. The threonine at codon 24 is replaced by isoleucine, an amino acid with similar properties. This variant has been detected in an individual from a dilated cardiomyopathy cohort (van Spaendonck-Zwarts KY et al. Eur J Heart Fail, 2013 Jun;15:628-36). This amino acid position is well 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.
Invitae	RCV003745339	SCV004445792	uncertain significance	Charcot-Marie-Tooth disease type 2	2023-12-28	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 24 of the LMNA protein (p.Thr24Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LMNA-related conditions. ClinVar contains an entry for this variant (Variation ID: 1174962). 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 with a positive predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
All of Us Research Program, National Institutes of Health	RCV004008915	SCV004837664	uncertain significance	Primary dilated cardiomyopathy	2023-11-30	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529465	SCV001742972	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001529465	SCV001953914	uncertain significance	not provided		no assertion criteria provided	clinical testing