NM_053025.4(MYLK):c.3610C>T (p.Arg1204Trp) AND Familial thoracic aortic aneurysm and aortic dissection

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 3, 2021
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:: RCV001170120.5

Allele description [Variation Report for NM_053025.4(MYLK):c.3610C>T (p.Arg1204Trp)]

NM_053025.4(MYLK):c.3610C>T (p.Arg1204Trp)

Gene:

MYLK:myosin light chain kinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q21.1

Genomic location:

Preferred name:

NM_053025.4(MYLK):c.3610C>T (p.Arg1204Trp)

HGVS:

NC_000003.12:g.123682266G>A
NG_029111.1:g.207037C>T
NM_001321309.2:c.3082C>T
NM_053025.4:c.3610C>TMANE SELECT
NM_053026.4:c.3403C>T
NM_053027.4:c.3610C>T
NM_053028.4:c.3403C>T
NP_001308238.1:p.Arg1028Trp
NP_444253.3:p.Arg1204Trp
NP_444254.3:p.Arg1135Trp
NP_444255.3:p.Arg1204Trp
NP_444256.3:p.Arg1135Trp
NC_000003.11:g.123401113G>A
NM_053025.3:c.3610C>T

Protein change:

R1028W

Links:

dbSNP: rs151294221

NCBI 1000 Genomes Browser:

rs151294221

Molecular consequence:

NM_001321309.2:c.3082C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_053025.4:c.3610C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_053026.4:c.3403C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_053027.4:c.3610C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_053028.4:c.3403C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial thoracic aortic aneurysm and aortic dissection (TAAD)
Synonyms:: Thoracic aortic aneurysm and aortic dissection; Thoracic aortic aneurysms and dissections
Identifiers:: MONDO: MONDO:0019625; MedGen: C4707243; Orphanet: 91387; OMIM: PS607086

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001332659	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 9, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002617454	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Aug 3, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001332659

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 9, 2020)

germline

clinical testing

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

SCV002617454

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Aug 3, 2021)

germline

clinical testing

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

Citation Link

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

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

Results of next-generation sequencing gene panel diagnostics including copy-number variation analysis in 810 patients suspected of heritable thoracic aortic disorders.

Overwater E, Marsili L, Baars MJH, Baas AF, van de Beek I, Dulfer E, van Hagen JM, Hilhorst-Hofstee Y, Kempers M, Krapels IP, Menke LA, Verhagen JMA, Yeung KK, Zwijnenburg PJG, Groenink M, van Rijn P, Weiss MM, Voorhoeve E, van Tintelen JP, Houweling AC, Maugeri A.

Hum Mutat. 2018 Sep;39(9):1173-1192. doi: 10.1002/humu.23565. Epub 2018 Jul 12.

PubMed [citation]

PMID:: 29907982
PMCID:: PMC6175145

Details of each submission

From CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario, SCV001332659.2

#	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

From Ambry Genetics, SCV002617454.2

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

Description

The p.R1204W variant (also known as c.3610C>T), located in coding exon 17 of the MYLK gene, results from a C to T substitution at nucleotide position 3610. The arginine at codon 1204 is replaced by tryptophan, an amino acid with dissimilar properties. This alteration has been reported in a thoracic aortic aneurysm and dissection (TAAD) cohort (Overwater E et al. Hum Mutat, 2018 09;39:1173-1192). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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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