NM_170707.4(LMNA):c.1157+1G>T AND Charcot-Marie-Tooth disease type 2

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 11, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001857811.5

Allele description [Variation Report for NM_170707.4(LMNA):c.1157+1G>T]

NM_170707.4(LMNA):c.1157+1G>T

Gene:

LMNA:lamin A/C [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q22

Genomic location:

Preferred name:

NM_170707.4(LMNA):c.1157+1G>T

HGVS:

NC_000001.11:g.156136122G>T
NG_008692.2:g.58550G>T
NM_001257374.3:c.821+1G>T
NM_001282624.2:c.914+1G>T
NM_001282625.2:c.1157+1G>T
NM_001282626.2:c.1157+1G>T
NM_001406983.1:c.1157+1G>T
NM_001406984.1:c.1157+1G>T
NM_001406985.1:c.1157+1G>T
NM_001406986.1:c.914+1G>T
NM_001406987.1:c.914+1G>T
NM_001406988.1:c.860+1G>T
NM_001406989.1:c.821+1G>T
NM_001406990.1:c.599+1G>T
NM_001406991.1:c.1157+1G>T
NM_001406992.1:c.1157+1G>T
NM_001406993.1:c.599+1G>T
NM_001406994.1:c.533+1G>T
NM_001406995.1:c.599+1G>T
NM_001406996.1:c.599+1G>T
NM_001406997.1:c.599+1G>T
NM_001406998.1:c.821+1G>T
NM_001406999.1:c.533+1G>T
NM_001407000.1:c.533+1G>T
NM_001407001.1:c.533+1G>T
NM_001407002.1:c.599+1G>T
NM_001407003.1:c.599+1G>T
NM_005572.4:c.1157+1G>T
NM_170707.4:c.1157+1G>TMANE SELECT
NM_170708.4:c.1157+1G>T
LRG_254t2:c.1157+1G>T
LRG_254:g.58550G>T
NC_000001.10:g.156105913G>T
NM_170707.2:c.1157+1G>T

Links:

dbSNP: rs267607590

NCBI 1000 Genomes Browser:

rs267607590

Molecular consequence:

NM_001257374.3:c.821+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001282624.2:c.914+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001282625.2:c.1157+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001282626.2:c.1157+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406983.1:c.1157+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406984.1:c.1157+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406985.1:c.1157+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406986.1:c.914+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406987.1:c.914+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406988.1:c.860+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406989.1:c.821+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406990.1:c.599+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406991.1:c.1157+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406992.1:c.1157+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406993.1:c.599+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406994.1:c.533+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406995.1:c.599+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406996.1:c.599+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406997.1:c.599+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406998.1:c.821+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406999.1:c.533+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407000.1:c.533+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407001.1:c.533+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407002.1:c.599+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407003.1:c.599+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_005572.4:c.1157+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_170707.4:c.1157+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_170708.4:c.1157+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Charcot-Marie-Tooth disease type 2
Synonyms:: Charcot-Marie-Tooth, Type 2
Identifiers:: MONDO: MONDO:0018993; MedGen: C0270914

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002260409	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 11, 2021)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 22224630, 24034385, 28878402, 16199547, 18585512, 18926329, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002260409

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 11, 2021)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Identification of novel mutations in LMNA associated with familial forms of dilated cardiomyopathy.

Stallmeyer B, Koopmann M, Schulze-Bahr E.

Genet Test Mol Biomarkers. 2012 Jun;16(6):543-9. doi: 10.1089/gtmb.2011.0214. Epub 2012 Jan 6.

PubMed [citation]

PMID:: 22224630

Hutchinson-Gilford progeria syndrome: report of 2 cases and a novel LMNA mutation of HGPS in China.

Zhang H, Chen X, Guo Y, Liang J, Tang L, Yu H, Yao Z.

J Am Acad Dermatol. 2013 Oct;69(4):e175-6. doi: 10.1016/j.jaad.2011.07.002. No abstract available.

PubMed [citation]

PMID:: 24034385

See all PubMed Citations (7)

Details of each submission

From Invitae, SCV002260409.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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. This variant has been observed in individual(s) with clinical features of LMNA-related conditions (PMID: 22224630, 24034385, 28878402). This variant is also known as IVS6+1G>T. ClinVar contains an entry for this variant (Variation ID: 246075). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 6 of the LMNA gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in LMNA are known to be pathogenic (PMID: 18585512, 18926329).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 20, 2024

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