Submissions for variant NM_170707.4(LMNA):c.895A>G (p.Ile299Val)

gnomAD frequency: 0.00016  dbSNP: rs150924946

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041378	SCV000065071	uncertain significance	not specified	2019-03-07	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Ile299Val variant in LMNA has been reported in 1 individual with Familial Partial Lipodystrophy (FPLD2) and lipomas (it is unclear if this individual had any cardiac manifestations), segregated with disease in 2 affected relatives but was also detected in 1 assymptomatic nephew of the proband, and was absent from 100 control chromosomes (Araújo-Vilar 2011). It has also been reported in 1 individual with DCM (Pugh 2014). This variant has also been identified in 0.3% of Latino chromosomes in gnomAD. Conserved across evolutionarily distant species, however computational predictions on the impact to the protein are mixed . This data suggests that the Ile299Val variant may be benign for cardiomyopathy and Familial Partial Lipodystrophy, although additional information is needed to fully assess its clinical significance.
Invitae	RCV001086902	SCV000218516	likely benign	Charcot-Marie-Tooth disease type 2	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000726532	SCV000234686	likely benign	not provided	2021-01-18	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 28663758, 25163546, 25351510, 25367549, 25637381, 24503780, 21883346, 27841971, 26332594, 25832542)
Eurofins Ntd Llc (ga)	RCV000726532	SCV000345279	uncertain significance	not provided	2017-06-26	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000619864	SCV000735968	likely benign	Cardiovascular phenotype	2017-11-17	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Color Diagnostics, LLC DBA Color Health	RCV000777745	SCV000913706	likely benign	Cardiomyopathy	2018-09-10	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000726532	SCV001144442	benign	not provided	2018-09-07	criteria provided, single submitter	clinical testing
Molecular Genetics Laboratory, London Health Sciences Centre	RCV001174244	SCV001337373	uncertain significance	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000041378	SCV002500133	likely benign	not specified	2022-03-05	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000726532	SCV003814735	uncertain significance	not provided	2022-06-07	criteria provided, single submitter	clinical testing
CSER _CC_NCGL, University of Washington	RCV000148604	SCV000190319	uncertain significance	Familial partial lipodystrophy, Dunnigan type	2014-06-01	no assertion criteria provided	research