NM_170707.4(LMNA):c.317T>C (p.Leu106Pro) AND Charcot-Marie-Tooth disease type 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 29, 2022
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:: RCV003030763.3

Allele description [Variation Report for NM_170707.4(LMNA):c.317T>C (p.Leu106Pro)]

NM_170707.4(LMNA):c.317T>C (p.Leu106Pro)

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.317T>C (p.Leu106Pro)

HGVS:

NC_000001.11:g.156115235T>C
NG_008692.2:g.37663T>C
NM_001282625.2:c.317T>C
NM_001282626.2:c.317T>C
NM_001406983.1:c.317T>C
NM_001406984.1:c.317T>C
NM_001406985.1:c.317T>C
NM_001406986.1:c.-107T>C
NM_001406990.1:c.-85T>C
NM_001406991.1:c.317T>C
NM_001406992.1:c.317T>C
NM_001406994.1:c.-348T>C
NM_001406995.1:c.-85T>C
NM_001406999.1:c.-528T>C
NM_001407000.1:c.-348T>C
NM_001407001.1:c.-191T>C
NM_001407002.1:c.-85T>C
NM_005572.4:c.317T>C
NM_170707.4:c.317T>CMANE SELECT
NM_170708.4:c.317T>C
NP_001269554.1:p.Leu106Pro
NP_001269555.1:p.Leu106Pro
NP_001393912.1:p.Leu106Pro
NP_001393913.1:p.Leu106Pro
NP_001393914.1:p.Leu106Pro
NP_001393920.1:p.Leu106Pro
NP_001393921.1:p.Leu106Pro
NP_005563.1:p.Leu106Pro
NP_005563.1:p.Leu106Pro
NP_733821.1:p.Leu106Pro
NP_733821.1:p.Leu106Pro
NP_733822.1:p.Leu106Pro
NP_733822.1:p.Leu106Pro
LRG_254t1:c.317T>C
LRG_254t2:c.317T>C
LRG_254t3:c.317T>C
LRG_254:g.37663T>C
LRG_254p1:p.Leu106Pro
LRG_254p2:p.Leu106Pro
LRG_254p3:p.Leu106Pro
NC_000001.10:g.156085026T>C
NM_005572.3:c.317T>C
NM_170707.2:c.317T>C
NM_170708.2:c.317T>C
NR_047544.1:n.958T>C

Protein change:

L106P

Molecular consequence:

NM_001282625.2:c.317T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001282626.2:c.317T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406983.1:c.317T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406984.1:c.317T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406985.1:c.317T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406991.1:c.317T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406992.1:c.317T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_005572.4:c.317T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_170707.4:c.317T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_170708.4:c.317T>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV003310501	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 29, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32571898, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003310501

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 29, 2022)

germline

clinical testing

PubMed (2)
[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

Clinical spectrum and genetic variations of LMNA-related muscular dystrophies in a large cohort of Chinese patients.

Fan Y, Tan D, Song D, Zhang X, Chang X, Wang Z, Zhang C, Chan SH, Wu Q, Wu L, Wang S, Yan H, Ge L, Yang H, Mao B, Bönnemann C, Liu J, Wang S, Yuan Y, Wu X, Zhang H, Xiong H.

J Med Genet. 2021 May;58(5):326-333. doi: 10.1136/jmedgenet-2019-106671. Epub 2020 Jun 22.

PubMed [citation]

PMID:: 32571898
PMCID:: PMC8086255

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003310501.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt LMNA protein function. This missense change has been observed in individual(s) with autosomal dominant Emery-Dreifuss muscular dystrophy (PMID: 32571898). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 106 of the LMNA protein (p.Leu106Pro).

#	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: Sep 29, 2024

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