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NM_020549.5(CHAT):c.1441dup (p.Arg481fs) AND Familial infantile myasthenia

Germline classification:
Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:
Nov 27, 2023
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:
RCV003468381.2

Allele description [Variation Report for NM_020549.5(CHAT):c.1441dup (p.Arg481fs)]

NM_020549.5(CHAT):c.1441dup (p.Arg481fs)

Gene:
CHAT:choline O-acetyltransferase [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
10q11.23
Genomic location:
Preferred name:
NM_020549.5(CHAT):c.1441dup (p.Arg481fs)
HGVS:
  • NC_000010.11:g.49649566dup
  • NG_011797.1:g.45472dup
  • NG_011797.2:g.45473dup
  • NG_119463.1:g.783dup
  • NM_001142929.2:c.1087dup
  • NM_001142933.2:c.1195dup
  • NM_001142934.2:c.1087dup
  • NM_020549.5:c.1441dupMANE SELECT
  • NM_020984.4:c.1087dup
  • NM_020985.4:c.1087dup
  • NM_020986.4:c.1087dup
  • NP_001136401.2:p.Arg363fs
  • NP_001136405.2:p.Arg399fs
  • NP_001136406.2:p.Arg363fs
  • NP_065574.4:p.Arg481fs
  • NP_066264.4:p.Arg363fs
  • NP_066265.4:p.Arg363fs
  • NP_066266.4:p.Arg363fs
  • NC_000010.10:g.50857606_50857607insC
  • NC_000010.10:g.50857612dup
Protein change:
R363fs
Molecular consequence:
  • NM_001142929.2:c.1087dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001142933.2:c.1195dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001142934.2:c.1087dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_020549.5:c.1441dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_020984.4:c.1087dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_020985.4:c.1087dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_020986.4:c.1087dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Familial infantile myasthenia (CMS6)
Synonyms:
Congenital myasthenic syndrome with episodic apnea; Myasthenic syndrome congenital associated with episodic apnea; Myasthenic syndrome, presynaptic, congenital, associated with episodic apnea; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009689; MedGen: C0393929; Orphanet: 590; OMIM: 254210

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004215800Baylor Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Oct 11, 2023)
unknownclinical testing

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

SCV004538412Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Nov 27, 2023)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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

Choline acetyltransferase mutations in myasthenic syndrome due to deficient acetylcholine resynthesis.

Maselli RA, Chen D, Mo D, Bowe C, Fenton G, Wollmann RL.

Muscle Nerve. 2003 Feb;27(2):180-7.

PubMed [citation]
PMID:
12548525
See all PubMed Citations (5)

Details of each submission

From Baylor Genetics, SCV004215800.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV004538412.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Arg481Profs*30) in the CHAT gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHAT are known to be pathogenic (PMID: 12548525, 21786365, 23292760). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CHAT-related conditions. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Feb 28, 2024