NM_002474.3(MYH11):c.1951C>T (p.Arg651Cys) AND Aortic aneurysm, familial thoracic 4

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 22, 2023
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:: RCV002010572.4

Allele description [Variation Report for NM_002474.3(MYH11):c.1951C>T (p.Arg651Cys)]

NM_002474.3(MYH11):c.1951C>T (p.Arg651Cys)

Gene:

MYH11:myosin heavy chain 11 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.11

Genomic location:

Preferred name:

NM_002474.3(MYH11):c.1951C>T (p.Arg651Cys)

HGVS:

NC_000016.10:g.15750245G>A
NG_009299.1:g.111786C>T
NM_001040113.2:c.1972C>T
NM_001040114.2:c.1972C>T
NM_002474.3:c.1951C>TMANE SELECT
NM_022844.3:c.1951C>T
NP_001035202.1:p.Arg658Cys
NP_001035203.1:p.Arg658Cys
NP_002465.1:p.Arg651Cys
NP_074035.1:p.Arg651Cys
LRG_1401t1:c.1951C>T
LRG_1401t2:c.1972C>T
LRG_1401:g.111786C>T
LRG_1401p1:p.Arg651Cys
LRG_1401p2:p.Arg658Cys
NC_000016.9:g.15844102G>A

Protein change:

R651C

Links:

dbSNP: rs1160451543

NCBI 1000 Genomes Browser:

rs1160451543

Molecular consequence:

NM_001040113.2:c.1972C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001040114.2:c.1972C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002474.3:c.1951C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_022844.3:c.1951C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Aortic aneurysm, familial thoracic 4 (AAT4)
Synonyms:: Aortic aneurysm/aortic dissection and patent ductus arteriosus
Identifiers:: MONDO: MONDO:0007568; MedGen: C1851504; OMIM: 132900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002290491	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 22, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30739908, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002290491

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 22, 2023)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genetic diversity and pathogenic variants as possible predictors of severity in a French sample of nonsyndromic heritable thoracic aortic aneurysms and dissections (nshTAAD).

Arnaud P, Hanna N, Benarroch L, Aubart M, Bal L, Bouvagnet P, Busa T, Dulac Y, Dupuis-Girod S, Edouard T, Faivre L, Gouya L, Lacombe D, Langeois M, Leheup B, Milleron O, Naudion S, Odent S, Tchitchinadze M, Ropers J, Jondeau G, Boileau C.

Genet Med. 2019 Sep;21(9):2015-2024. doi: 10.1038/s41436-019-0444-y. Epub 2019 Feb 11.

PubMed [citation]

PMID:: 30739908

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, SCV002290491.3

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

Description

This missense change has been observed in individual(s) with non-syndromic heritable thoracic aortic aneurysms and dissections (PMID: 30739908). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MYH11 protein function. ClinVar contains an entry for this variant (Variation ID: 1499306). This variant is present in population databases (no rsID available, gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 658 of the MYH11 protein (p.Arg658Cys).

#	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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