NM_005677.4(COLQ):c.661C>T (p.Pro221Ser) AND Congenital myasthenic syndrome 5

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 18, 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:: RCV001298753.6

Allele description [Variation Report for NM_005677.4(COLQ):c.661C>T (p.Pro221Ser)]

NM_005677.4(COLQ):c.661C>T (p.Pro221Ser)

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.661C>T (p.Pro221Ser)

HGVS:

NC_000003.12:g.15470592G>A
NG_009032.2:g.56160C>T
NM_005677.4:c.661C>TMANE SELECT
NM_080538.2:c.631C>T
NM_080539.4:c.559C>T
NP_005668.2:p.Pro221Ser
NP_536799.1:p.Pro211Ser
NP_536800.2:p.Pro187Ser
NC_000003.11:g.15512099G>A
NG_009032.1:g.56160C>T

Protein change:

P187S

Links:

dbSNP: rs2062265717

NCBI 1000 Genomes Browser:

rs2062265717

Molecular consequence:

NM_005677.4:c.661C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_080538.2:c.631C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_080539.4:c.559C>T - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001487820	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 18, 2022)	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

SCV001487820

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 18, 2022)

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

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

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001487820.3

#	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 proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 221 of the COLQ protein (p.Pro221Ser). This variant is not present in population databases (gnomAD no frequency). 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: 1002338). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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: Sep 29, 2024

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