Submissions for variant NM_170707.4(LMNA):c.1566C>T (p.Cys522=)

gnomAD frequency: 0.00123  dbSNP: rs149339264

Total submissions: 27

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041322	SCV000065015	benign	not specified	2012-04-10	criteria provided, single submitter	clinical testing	Cys522Cys in Exon 09 of LMNA: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence and has been identified in 0.4% (16/3736) of Afric an American chromosomes from a broad population by the NHLBI Exome Sequencing Pr oject (http://evs.gs.washington.edu/EVS; dbSNP rs149339264).
GeneDx	RCV000041322	SCV000234660	benign	not specified	2014-09-04	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.
Invitae	RCV000233927	SCV000291552	benign	Charcot-Marie-Tooth disease type 2	2024-01-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000242680	SCV000320506	likely benign	Cardiovascular phenotype	2016-02-01	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.
Eurofins Ntd Llc (ga)	RCV000041322	SCV000331131	likely benign	not specified	2015-08-20	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000262946	SCV000348915	likely benign	Dilated cardiomyopathy 1A	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000320484	SCV000348916	likely benign	Familial partial lipodystrophy, Dunnigan type	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000377490	SCV000348917	likely benign	Lipoatrophy with Diabetes, Hepatic Steatosis, Hypertrophic Cardiomyopathy, and Leukomelanodermic Papules	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000289458	SCV000348918	likely benign	Emery-Dreifuss muscular dystrophy	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000285909	SCV000348919	likely benign	Hutchinson-Gilford syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000380292	SCV000348920	likely benign	Congenital muscular dystrophy due to LMNA mutation	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000340752	SCV000348922	likely benign	Mandibuloacral dysplasia with type A lipodystrophy	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000399953	SCV000348923	likely benign	Lethal tight skin contracture syndrome	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000337260	SCV000348925	likely benign	Limb-Girdle Muscular Dystrophy, Recessive	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001093764	SCV000348926	likely benign	Charcot-Marie-Tooth disease type 2B1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Genetic Services Laboratory, University of Chicago	RCV000041322	SCV000595609	uncertain significance	not specified	2013-02-08	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000777760	SCV000913725	benign	Cardiomyopathy	2018-10-15	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000041322	SCV000917596	benign	not specified	2018-07-09	criteria provided, single submitter	clinical testing	Variant summary: LMNA c.1566C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00052 in 259802 control chromosomes (gnomAD). The observed variant frequency is approximately 2-fold of the estimated maximal expected allele frequency for a pathogenic variant in LMNA causing Cardiomyopathy phenotype (0.00025), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1566C>T in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Illumina Laboratory Services, Illumina	RCV001098994	SCV001255401	likely benign	Emery-Dreifuss muscular dystrophy 2, autosomal dominant	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Molecular Genetics Laboratory, London Health Sciences Centre	RCV001172631	SCV001335694	likely benign	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000041322	SCV001476535	benign	not specified	2020-01-24	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001310873	SCV001500845	likely benign	not provided	2023-11-01	criteria provided, single submitter	clinical testing	LMNA: BP4, BP7
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV000262946	SCV003928189	uncertain significance	Dilated cardiomyopathy 1A		criteria provided, single submitter	research	Potent mutations in LMNA gene can lead to structural alteration in skeletal and cardiac muscle by altering the structure of Lamin A and Lamin C. It is associated with dilated cardiomyopathy and skeletal muscle dystrophies. However no sufficient evidence is found to ascertain the role of this particular variant rs149339264, yet.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001310873	SCV001740698	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000041322	SCV001923143	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001310873	SCV001964285	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001310873	SCV002036556	likely benign	not provided		no assertion criteria provided	clinical testing