Submissions for variant NM_170707.4(LMNA):c.1488G>A (p.Thr496=) (rs375516745)

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Clinical Services Laboratory,Illumina	RCV000364565	SCV000348891	likely benign	Charcot-Marie-Tooth disease, type 2	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000272434	SCV000348892	likely benign	Mandibuloacral dysplasia	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000329882	SCV000348893	likely benign	Dilated Cardiomyopathy, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000387328	SCV000348894	likely benign	Limb-Girdle Muscular Dystrophy, Recessive	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000295329	SCV000348895	likely benign	Familial partial lipodystrophy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000279873	SCV000348896	likely benign	Hutchinson-Gilford syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000279873	SCV000348897	likely benign	Hutchinson-Gilford syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000279873	SCV000348898	likely benign	Hutchinson-Gilford syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000337310	SCV000348899	likely benign	Lipoatrophy with Diabetes, Hepatic Steatosis, Hypertrophic Cardiomyopathy, and Leukomelanodermic Papules	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000399235	SCV000348900	likely benign	Congenital muscular dystrophy, LMNA-related	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000283389	SCV000348901	likely benign	Emery-Dreifuss muscular dystrophy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000341138	SCV000348902	likely benign	Lethal tight skin contracture syndrome	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000424743	SCV000513497	benign	not specified	2015-05-08	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics	RCV000733840	SCV000861941	uncertain significance	not provided	2018-06-21	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario	RCV000769730	SCV000901151	likely benign	Cardiomyopathy	2017-10-06	criteria provided, single submitter	clinical testing
Color	RCV000769730	SCV000913459	likely benign	Cardiomyopathy	2018-03-05	criteria provided, single submitter	clinical testing
Invitae	RCV000364565	SCV000942361	uncertain significance	Charcot-Marie-Tooth disease, type 2	2018-12-06	criteria provided, single submitter	clinical testing	This sequence change affects codon 496 of the LMNA mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the LMNA protein. This variant also falls at the last nucleotide of exon 8 of the LMNA coding sequence, which is part of the consensus splice site for this exon. This variant is present in population databases (rs375516745, ExAC 0.01%). This variant has not been reported in the literature in individuals with LMNA-related conditions. ClinVar contains an entry for this variant (Variation ID: 292839). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.