NM_002474.3(MYH11):c.5737A>C (p.Ser1913Arg) AND Familial thoracic aortic aneurysm and aortic dissection

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 4, 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:: RCV001183828.6

Allele description [Variation Report for NM_002474.3(MYH11):c.5737A>C (p.Ser1913Arg)]

NM_002474.3(MYH11):c.5737A>C (p.Ser1913Arg)

Genes:

MYH11:myosin heavy chain 11 [Gene - OMIM - HGNC]
NDE1:nudE neurodevelopment protein 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.11

Genomic location:

Preferred name:

NM_002474.3(MYH11):c.5737A>C (p.Ser1913Arg)

HGVS:

NC_000016.10:g.15714958T>G
NG_009299.1:g.147073A>C
NG_021210.1:g.76692T>G
NM_001040113.2:c.5758A>C
NM_001040114.2:c.5758A>C
NM_001143979.2:c.948-9233T>G
NM_002474.3:c.5737A>CMANE SELECT
NM_017668.3:c.948-9233T>GMANE SELECT
NM_022844.3:c.5737A>C
NP_001035202.1:p.Ser1920Arg
NP_001035203.1:p.Ser1920Arg
NP_002465.1:p.Ser1913Arg
NP_074035.1:p.Ser1913Arg
LRG_1401t1:c.5737A>C
LRG_1401t2:c.5758A>C
LRG_1401:g.147073A>C
LRG_1401p1:p.Ser1913Arg
LRG_1401p2:p.Ser1920Arg
NC_000016.9:g.15808815T>G
NC_000016.9:g.15808815T>G
NM_001040113.1:c.5758A>C
NM_002474.2:c.5737A>C

Protein change:

S1913R

Links:

dbSNP: rs760586766

NCBI 1000 Genomes Browser:

rs760586766

Molecular consequence:

NM_001143979.2:c.948-9233T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_017668.3:c.948-9233T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001040113.2:c.5758A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001040114.2:c.5758A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002474.3:c.5737A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_022844.3:c.5737A>C - 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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Homo sapiens phosphatidylinositol glycan anchor biosynthesis class M (PIGM), Ref...
Homo sapiens phosphatidylinositol glycan anchor biosynthesis class M (PIGM), RefSeqGene on chromosome 1
gi|238637290|ref|NG_012238.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001349670	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 4, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002649674	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Nov 5, 2021)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001349670

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Dec 4, 2023)

germline

clinical testing

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

SCV002649674

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Nov 5, 2021)

germline

clinical testing

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

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001349670.3

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

Description

Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the coiled coil myosin tail domain of the MYH11 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant is rare in the general population and has been identified in 0/277264 chromosomes by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.

#	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, SCV002649674.2

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

Description

The p.S1913R variant (also known as c.5737A>C), located in coding exon 39 of the MYH11 gene, results from an A to C substitution at nucleotide position 5737. The serine at codon 1913 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. 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: Sep 29, 2024

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