VCV000036479.70 - ClinVar

NM_170707.4(LMNA):c.51C>T (p.Ser17=)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(35)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_170707.4(LMNA):c.51C>T (p.Ser17=)

Variation ID: 36479 Accession: VCV000036479.70

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 1q22 1: 156114969 (GRCh38) [ NCBI UCSC ] 1: 156084760 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Apr 4, 2013	Oct 20, 2024	Aug 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_170707.4:c.51C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_733821.1:p.Ser17=	synonymous
NM_005572.4:c.51C>T MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_005563.1:p.Ser17=	synonymous
NM_001282625.2:c.51C>T	NP_001269554.1:p.Ser17=	synonymous
NM_001282626.2:c.51C>T	NP_001269555.1:p.Ser17=	synonymous
NM_170708.4:c.51C>T	NP_733822.1:p.Ser17=	synonymous
NC_000001.11:g.156114969C>T
NC_000001.10:g.156084760C>T
NG_008692.2:g.37397C>T
LRG_254:g.37397C>T
LRG_254t1:c.51C>T	LRG_254p1:p.Ser17=
LRG_254t2:c.51C>T
LRG_254t3:c.51C>T

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000001.11:156114968:C:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00679 (T)

Allele frequency Help The frequency of the allele represented by this VCV record.

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00945

Trans-Omics for Precision Medicine (TOPMed) 0.00989

The Genome Aggregation Database (gnomAD), exomes 0.01044

1000 Genomes Project 30x 0.00640

1000 Genomes Project 0.00679

The Genome Aggregation Database (gnomAD) 0.00797

Exome Aggregation Consortium (ExAC) 0.02399

Links

ClinGen: CA018206 dbSNP: rs11549668 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
LMNA		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	1847	2129
LOC129931597	-	-	-	GRCh38	-	103

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Primary dilated cardiomyopathy	Benign (1)	no assertion criteria provided	Aug 18, 2011	RCV000030151.9
not specified	Benign (9)	criteria provided, multiple submitters, no conflicts	May 30, 2020	RCV000041354.42
not provided	Benign/Likely benign (6)	criteria provided, multiple submitters, no conflicts	Aug 1, 2024	RCV000057414.39
Charcot-Marie-Tooth disease type 2	Benign (1)	criteria provided, single submitter	Feb 1, 2024	RCV000204379.21
Cardiovascular phenotype	Benign (1)	criteria provided, single submitter	Dec 14, 2012	RCV000246550.9
Cardiomyopathy	Benign (2)	criteria provided, multiple submitters, no conflicts	Mar 15, 2018	RCV000768708.12
Familial partial lipodystrophy, Dunnigan type	Benign (1)	criteria provided, single submitter	Jan 13, 2018	RCV000385116.13
Dilated cardiomyopathy 1A	Likely benign (2)	criteria provided, single submitter	Jan 13, 2018	RCV001028068.13
Charcot-Marie-Tooth disease type 2B1	Benign (1)	criteria provided, single submitter	Jan 13, 2018	RCV001093839.12
Emery-Dreifuss muscular dystrophy 2, autosomal dominant	Benign (1)	criteria provided, single submitter	Jan 13, 2018	RCV001098001.12
Limb-girdle muscular dystrophy, recessive	Likely benign (1)	criteria provided, single submitter	Jun 14, 2016	RCV000265426.13
Mandibuloacral dysplasia with type A lipodystrophy	Benign (1)	criteria provided, single submitter	Jan 13, 2018	RCV000350387.13
Congenital muscular dystrophy due to LMNA mutation	Benign (1)	criteria provided, single submitter	Jan 13, 2018	RCV000351657.13
Lethal tight skin contracture syndrome	Benign (1)	criteria provided, single submitter	Jan 13, 2018	RCV000285289.13
Hutchinson-Gilford syndrome	Likely benign (1)	criteria provided, single submitter	Jun 14, 2016	RCV000290770.14
Lipoatrophy with Diabetes, Hepatic Steatosis, Hypertrophic Cardiomyopathy, and Leukomelanodermic Papules	Benign (1)	criteria provided, single submitter	Jan 13, 2018	RCV000320485.13
Emery-Dreifuss muscular dystrophy	Benign (1)	criteria provided, single submitter	Jan 13, 2018	RCV000355480.13
Charcot-Marie-Tooth disease	Benign (1)	criteria provided, single submitter	-	RCV001173421.9
Charcot-Marie-Tooth disease type 2B1 Congenital muscular dystrophy due to LMNA mutation Dilated cardiomyopathy 1A Dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome Emery-Dreifuss muscular dystrophy 2, autosomal dominant Emery-Dreifuss muscular dystrophy 3, autosomal recessive Familial partial lipodystrophy, Dunnigan type Heart-hand syndrome, Slovenian type Hutchinson-Gilford syndrome Mandibuloacral dysplasia with type A lipodystrophy Restrictive dermopathy 2	Benign (1)	criteria provided, single submitter	Apr 17, 2022	RCV002496461.8
Hypertrophic cardiomyopathy 2	Likely benign (1)	no assertion criteria provided	-	RCV004595890.1
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Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (Nov 04, 2013)	criteria provided, single submitter (ACMG Guidelines, 2007) Method: clinical testing	not specified (Autosomal dominant inheritance) Affected status: unknown Allele origin: germline	Genetic Services Laboratory, University of Chicago Accession: SCV000193523.1 First in ClinVar: Nov 23, 2014 Last updated: Nov 23, 2014 Comment: Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated … (more) Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed (less)
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000316411.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Benign (Nov 21, 2023)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV001158851.6 First in ClinVar: Feb 10, 2020 Last updated: Feb 20, 2024
Benign (Aug 01, 2024)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV002496937.18 First in ClinVar: Apr 11, 2022 Last updated: Oct 20, 2024	Comment: LMNA: BP4, BP7, BS1, BS2 Number of individuals with the variant: 71
Likely benign (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Limb-Girdle Muscular Dystrophy, Recessive Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000348746.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Likely benign (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Progeroid Laminopathies Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000348752.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Benign (Aug 28, 2017)	criteria provided, single submitter (Athena Diagnostics Criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Athena Diagnostics Accession: SCV000842666.1 First in ClinVar: Oct 19, 2013 Last updated: Oct 19, 2013	Publications: PubMed (4) PubMed: 12920062‚ 19424285‚ 18795223‚ 19318026
Benign (May 30, 2013)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000113217.8 First in ClinVar: Jan 17, 2014 Last updated: Mar 08, 2017	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=LMNA Number of individuals with the variant: 2 Sex: mixed
Benign (Jan 13, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Mandibuloacral dysplasia with type A lipodystrophy Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000348753.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
Likely benign (Jan 13, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Dilated cardiomyopathy 1A Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000348750.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
Benign (Jan 13, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Lipoatrophy with Diabetes, Hepatic Steatosis, Hypertrophic Cardiomyopathy, and Leukomelanodermic Papules Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000348747.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
Benign (Jan 13, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Emery-Dreifuss muscular dystrophy Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000348745.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
Benign (Jan 13, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Charcot-Marie-Tooth disease type 2B1 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000348755.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
Benign (Jan 13, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Restrictive dermopathy 1 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000348749.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
Benign (Jan 13, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Familial partial lipodystrophy, Dunnigan type Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000348751.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
Benign (Jan 13, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Congenital muscular dystrophy due to LMNA mutation Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000348756.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Charcot-Marie-Tooth disease Affected status: yes Allele origin: germline	Molecular Genetics Laboratory, London Health Sciences Centre Accession: SCV001336509.1 First in ClinVar: Jun 15, 2020 Last updated: Jun 15, 2020
Benign (Oct 27, 2015)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Cardiomyopathy Affected status: unknown Allele origin: germline	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario Study: Canadian Open Genetics Repository Accession: SCV000900078.1 First in ClinVar: May 06, 2019 Last updated: May 06, 2019
Benign (Mar 15, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Cardiomyopathy Affected status: unknown Allele origin: germline	Color Diagnostics, LLC DBA Color Health Accession: SCV000902633.1 First in ClinVar: May 20, 2019 Last updated: May 20, 2019
Benign (Nov 26, 2012)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000065047.6 First in ClinVar: May 03, 2013 Last updated: Mar 08, 2017	Comment: Ser17Ser in exon 1 of LMNA: This variant is not expected to have clinical signif icance because it has been identified in 1.3% (108/8542) of … (more) Ser17Ser in exon 1 of LMNA: This variant is not expected to have clinical signif icance because it has been identified in 1.3% (108/8542) of European American ch romosomes from a broad population by the NHLBI Exome Sequencing Project (http:// evs.gs.washington.edu/EVS/; dbSNP rs11549668). (less) Number of individuals with the variant: 65
Benign (Jan 13, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Emery-Dreifuss muscular dystrophy 2, autosomal dominant Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001254335.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
Benign (May 30, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: yes Allele origin: germline	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute Accession: SCV001433201.1 First in ClinVar: Sep 27, 2020 Last updated: Sep 27, 2020
Benign (Dec 14, 2012)	criteria provided, single submitter (Ambry Autosomal Dominant and X-Linked criteria (10/2015)) Method: clinical testing	Cardiovascular phenotype Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000318011.5 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016	Comment: General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance Number of individuals with the variant: 1
Benign (Apr 17, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Dilated cardiomyopathy 1A Familial partial lipodystrophy, Dunnigan type Hutchinson-Gilford syndrome Emery-Dreifuss muscular dystrophy 2, autosomal dominant Emery-Dreifuss muscular dystrophy 2, autosomal dominant Dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome Mandibuloacral dysplasia with type A lipodystrophy Charcot-Marie-Tooth disease type 2B1 Heart-hand syndrome, Slovenian type Congenital muscular dystrophy due to LMNA mutation Emery-Dreifuss muscular dystrophy 3, autosomal recessive Restrictive dermopathy 2 Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002805393.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Benign (Feb 01, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Charcot-Marie-Tooth disease type 2 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000259730.10 First in ClinVar: Jan 31, 2016 Last updated: Feb 20, 2024
Likely benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005262254.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Benign (Aug 18, 2011)	no assertion criteria provided Method: clinical testing	Primary dilated cardiomyopathy Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000052806.2 First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013
Likely benign (-)	no assertion criteria provided Method: clinical testing	Hypertrophic cardiomyopathy 2 Affected status: yes Allele origin: unknown	Institute of Human Genetics, University of Wuerzburg Accession: SCV005088651.1 First in ClinVar: Aug 04, 2024 Last updated: Aug 04, 2024	Number of individuals with the variant: 1
Benign (Feb 05, 2020)	no assertion criteria provided Method: clinical testing	Dilated cardiomyopathy 1A Affected status: yes Allele origin: germline	Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City Accession: SCV001190848.1 First in ClinVar: Mar 29, 2020 Last updated: Mar 29, 2020
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001743740.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics, Academic Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001921523.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001957265.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001968486.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV002036936.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021
not provided (-)	no classification provided Method: not provided	not provided Affected status: not provided Allele origin: not provided	Epithelial Biology; Institute of Medical Biology, Singapore Accession: SCV000088528.1 First in ClinVar: Oct 19, 2013 Last updated: Oct 19, 2013
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Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

Comment:

Ser17Ser in exon 1 of LMNA: This variant is not expected to have clinical signif icance because it has been identified in 1.3% (108/8542) of European American ch romosomes from a broad population by the NHLBI Exome Sequencing Project (http:// evs.gs.washington.edu/EVS/; dbSNP rs11549668).

Comment:

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Mutations in the LMNA gene do not cause axonal CMT in Czech patients.	Lassuthová P	Journal of human genetics	2009	PMID: 19424285
Validation of high-resolution DNA melting analysis for mutation scanning of the LMNA gene.	Millat G	Clinical biochemistry	2009	PMID: 19318026
Identification of mutational hot spots in LMNA encoding lamin A/C in patients with familial dilated cardiomyopathy.	Perrot A	Basic research in cardiology	2009	PMID: 18795223
Expanding the phenotype of LMNA mutations in dilated cardiomyopathy and functional consequences of these mutations.	Sébillon P	Journal of medical genetics	2003	PMID: 12920062
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=LMNA	-	-	-	-

Text-mined citations for rs11549668 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_170707.4(LMNA):c.51C>T (p.Ser17=)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs11549668 ...