NM_005677.4(COLQ):c.391A>G (p.Lys131Glu) AND Congenital myasthenic syndrome 5

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Aug 23, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000687069.12

Allele description [Variation Report for NM_005677.4(COLQ):c.391A>G (p.Lys131Glu)]

NM_005677.4(COLQ):c.391A>G (p.Lys131Glu)

Gene:

COLQ:collagen like tail subunit of asymmetric acetylcholinesterase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p25.1

Genomic location:

Preferred name:

NM_005677.4(COLQ):c.391A>G (p.Lys131Glu)

HGVS:

NC_000003.12:g.15478979T>C
NG_009032.2:g.47773A>G
NM_005677.4:c.391A>GMANE SELECT
NM_080538.2:c.361A>G
NM_080539.4:c.289A>G
NP_005668.2:p.Lys131Glu
NP_536799.1:p.Lys121Glu
NP_536800.2:p.Lys97Glu
NC_000003.11:g.15520486T>C
NG_009032.1:g.47773A>G
NM_005677.3:c.391A>G

Protein change:

K121E

Links:

dbSNP: rs142980906

NCBI 1000 Genomes Browser:

rs142980906

Molecular consequence:

NM_005677.4:c.391A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_080538.2:c.361A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_080539.4:c.289A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Congenital myasthenic syndrome 5
Synonyms:: Endplate acetylcholinesterase deficiency
Identifiers:: MONDO: MONDO:0011281; MedGen: C1864233; Orphanet: 590; OMIM: 603034

Recent activity

Clear Turn Off Turn On

acidic fibroblast growth factor intracellular-binding protein isoform a [Homo sa...
acidic fibroblast growth factor intracellular-binding protein isoform a [Homo sapiens]
gi|38683849|ref|NP_942600.1|

Protein
acyl-coenzyme A thioesterase THEM4 [Mus musculus]
acyl-coenzyme A thioesterase THEM4 [Mus musculus]
gi|110626050|ref|NP_083707.1|

Protein
Mus musculus targeted non-conditional, lacZ-tagged mutant allele Pdxk:tm1e(EUCOM...
Mus musculus targeted non-conditional, lacZ-tagged mutant allele Pdxk:tm1e(EUCOMM)Wtsi tm1e(EUCOMM)Hmgu; transgenic
gi|354787068|gb|JN951569.1|

Nucleotide
Croton lindmanii (202)
Books
proton nitens (228)
ClinVar

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000814620	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 23, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001530367	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 14, 2018)	maternal	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003828321	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 14, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000814620

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 23, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001530367

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Aug 14, 2018)

maternal

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV003828321

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 14, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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
not provided	maternal	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000814620.6

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

Description

This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 131 of the COLQ protein (p.Lys131Glu). This variant is present in population databases (rs142980906, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with COLQ-related conditions. ClinVar contains an entry for this variant (Variation ID: 197779). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C55"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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

From Baylor Genetics, SCV001530367.1

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

Description

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].

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

From Revvity Omics, Revvity, SCV003828321.2

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

#	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: Oct 20, 2024

ClinVar

Relating variation to medicine