NM_000751.3(CHRND):c.340G>C (p.Val114Leu) AND Lethal multiple pterygium syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 17, 2024
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:: RCV003634026.1

Allele description

NM_000751.3(CHRND):c.340G>C (p.Val114Leu)

Gene:

CHRND:cholinergic receptor nicotinic delta subunit [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q37.1

Genomic location:

Preferred name:

NM_000751.3(CHRND):c.340G>C (p.Val114Leu)

HGVS:

NC_000002.12:g.232528358G>C
NG_008028.1:g.7147G>C
NM_000751.3:c.340G>CMANE SELECT
NM_001256657.2:c.295G>C
NM_001311195.2:c.69G>C
NM_001311196.2:c.50+19G>C
NP_000742.1:p.Val114Leu
NP_001243586.1:p.Val99Leu
NP_001298124.1:p.Leu23Phe
NC_000002.11:g.233393068G>C
NR_046333.1:n.396G>C

Protein change:

L23F

Molecular consequence:

NM_001311196.2:c.50+19G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000751.3:c.340G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001256657.2:c.295G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001311195.2:c.69G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Lethal multiple pterygium syndrome (LMPS)
Identifiers:: MONDO: MONDO:0009668; MedGen: C1854678; Orphanet: 33108; OMIM: 253290

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004557528	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 17, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 29399782, 32403337, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004557528

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 17, 2024)

germline

clinical testing

PubMed (3)
[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

Prenatal detection of uniparental disomy of chromosome 2 carrying a CHRND pathogenic variant that causes lethal multiple pterygium syndrome.

Shen W, Young BA, Bosworth M, Wright KE, Lamb AN, Ji Y.

Clin Genet. 2018 Jun;93(6):1248-1249. doi: 10.1111/cge.13164. Epub 2018 Feb 5. No abstract available.

PubMed [citation]

PMID:: 29399782

Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain.

Gonzalez-Quereda L, Rodriguez MJ, Diaz-Manera J, Alonso-Perez J, Gallardo E, Nascimento A, Ortez C, Natera-de Benito D, Olive M, Gonzalez-Mera L, Munain AL, Zulaica M, Poza JJ, Jerico I, Torne L, Riera P, Milisenda J, Sanchez A, Garrabou G, Llano I, Madruga-Garrido M, Gallano P.

Genes (Basel). 2020 May 11;11(5). doi:pii: E539. 10.3390/genes11050539.

PubMed [citation]

PMID:: 32403337
PMCID:: PMC7288461

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV004557528.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 114 of the CHRND protein (p.Val114Leu). This variant is present in population databases (rs760395222, gnomAD 0.002%). This missense change has been observed in individual(s) with clinical features of autosomal recessive CHRND-related conditions (PMID: 29399782, 32403337). 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 not expected to disrupt CHRND protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 28, 2024

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