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:
RCV001857811.6

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002260409Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Jan 11, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002260409.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024