Submissions for variant NM_170707.4(LMNA):c.438C>T (p.Ala146=)

gnomAD frequency: 0.00782  dbSNP: rs80356805

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041349	SCV000065042	benign	not specified	2012-07-06	criteria provided, single submitter	clinical testing	Ala146Ale in exon 2 of LMNA: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue, is not located within t he splice consensus sequence, and has been identified in 2.5% (108/4406) of Afri can American chromosomes from a broad population by the NHLBI Exome Sequencing P roject (http://evs.gs.washington.edu/EVS/; dbSNP rs80356805).
GeneDx	RCV000041349	SCV000170141	benign	not specified	2011-07-12	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.
Genetic Services Laboratory, University of Chicago	RCV000041349	SCV000193522	benign	not specified	2016-06-10	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004528232	SCV000316410	benign	LMNA-related disorder	2020-07-15	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Eurofins Ntd Llc (ga)	RCV000041349	SCV000331148	benign	not specified	2015-08-07	criteria provided, single submitter	clinical testing
Invitae	RCV001086851	SCV000559820	benign	Charcot-Marie-Tooth disease type 2	2024-01-31	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000041349	SCV000614030	benign	not specified	2017-07-27	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587594	SCV000699969	benign	not provided	2016-09-19	criteria provided, single submitter	clinical testing	Variant summary: The LMNA c.438C>T (p.Ala146Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 281/109760 control chromosomes (2 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.0277371 (265/9554). This frequency is about 111 times the estimated maximal expected allele frequency of a pathogenic LMNA variant (0.00025), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. Taken together, this variant is classified as Benign.
Ambry Genetics	RCV000617451	SCV000735849	benign	Cardiovascular phenotype	2016-04-16	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000768711	SCV000900081	benign	Cardiomyopathy	2015-10-09	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000768711	SCV000910955	benign	Cardiomyopathy	2018-03-15	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000587594	SCV002050075	likely benign	not provided	2021-09-27	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003996463	SCV004840613	benign	Primary dilated cardiomyopathy	2024-02-05	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000041349	SCV001916992	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000041349	SCV001951622	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000041349	SCV001976105	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000587594	SCV002036471	likely benign	not provided		no assertion criteria provided	clinical testing