NM_006901.4(MYO9A):c.608A>G (p.Tyr203Cys) AND Myasthenic syndrome, congenital, 24, presynaptic

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: May 26, 2020
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:: RCV000722149.3

Allele description [Variation Report for NM_006901.4(MYO9A):c.608A>G (p.Tyr203Cys)]

NM_006901.4(MYO9A):c.608A>G (p.Tyr203Cys)

Gene:

MYO9A:myosin IXA [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q23

Genomic location:

Preferred name:

NM_006901.4(MYO9A):c.608A>G (p.Tyr203Cys)

HGVS:

NC_000015.10:g.72045956T>C
NM_006901.4:c.608A>GMANE SELECT
NP_008832.2:p.Tyr203Cys
NC_000015.9:g.72338297T>C
NM_006901.1:c.608A>G
NM_006901.3:c.608A>G

Protein change:

Y203C; TYR203CYS

Links:

OMIM: 604875.0002; dbSNP: rs374155761

NCBI 1000 Genomes Browser:

rs374155761

Molecular consequence:

NM_006901.4:c.608A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Myasthenic syndrome, congenital, 24, presynaptic
Identifiers:: MONDO: MONDO:0032597; MedGen: C4748684; OMIM: 618198

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000854566	OMIM	no assertion criteria provided	Pathogenic (Nov 29, 2018)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002767109	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 26, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26752647, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000854566

OMIM

no assertion criteria provided

Pathogenic
(Nov 29, 2018)

germline

literature only

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

SCV002767109

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 26, 2020)

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular etiology of arthrogryposis in multiple families of mostly Turkish origin.

Bayram Y, Karaca E, Coban Akdemir Z, Yilmaz EO, Tayfun GA, Aydin H, Torun D, Bozdogan ST, Gezdirici A, Isikay S, Atik MM, Gambin T, Harel T, El-Hattab AW, Charng WL, Pehlivan D, Jhangiani SN, Muzny DM, Karaman A, Celik T, Yuregir OO, Yildirim T, et al.

J Clin Invest. 2016 Feb;126(2):762-78. doi: 10.1172/JCI84457. Epub 2016 Jan 11.

PubMed [citation]

PMID:: 26752647
PMCID:: PMC4731160

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 OMIM, SCV000854566.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

For discussion of the c.608A-G transition in the MYO9A gene, resulting in a tyr203-to-cys (Y203C) substitution, that was found in compound heterozygous state in a patient with congenital myasthenic syndrome-24 (CMS24; 618198) by Bayram et al. (2016) see 604875.0001.

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

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002767109.1

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

Description

Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as 3C-VUS. Following criteria are met: 0105 - The mechanism of disease for this gene is not clearly established. (N) 0106 - This gene is known to be associated with autosomal recessive disease. (N) 0200 - Variant is predicted to result in a missense amino acid change from tyrosine to cysteine (exon 2). (N) 0251 - Variant is heterozygous. (N) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (63 heterozygotes, 1 homozygote). (P) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (P) 0600 - Variant is located in an annotated domain or motif. In myosin head_motor domain (NCBI, PDB, DECIPHER) (N) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0808 - Previous reports of pathogenicity are conflicting. 1x VUS in ClinVar and seen in a patient cHet with p.(Gly2282Glu). (PMID: 26752647) (N) 1007 - No published functional evidence has been identified for this variant. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign

#	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

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