NM_002474.3(MYH11):c.5723A>C (p.Asp1908Ala) AND Aortic aneurysm, familial thoracic 4

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 6, 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:: RCV003629247.2

Allele description [Variation Report for NM_002474.3(MYH11):c.5723A>C (p.Asp1908Ala)]

NM_002474.3(MYH11):c.5723A>C (p.Asp1908Ala)

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.5723A>C (p.Asp1908Ala)

HGVS:

NC_000016.10:g.15714972T>G
NG_009299.1:g.147059A>C
NG_021210.1:g.76706T>G
NM_001040113.2:c.5744A>C
NM_001040114.2:c.5744A>C
NM_001143979.2:c.948-9219T>G
NM_002474.3:c.5723A>CMANE SELECT
NM_017668.3:c.948-9219T>GMANE SELECT
NM_022844.3:c.5723A>C
NP_001035202.1:p.Asp1915Ala
NP_001035203.1:p.Asp1915Ala
NP_002465.1:p.Asp1908Ala
NP_074035.1:p.Asp1908Ala
LRG_1401t1:c.5723A>C
LRG_1401t2:c.5744A>C
LRG_1401:g.147059A>C
LRG_1401p1:p.Asp1908Ala
LRG_1401p2:p.Asp1915Ala
NC_000016.9:g.15808829T>G
NM_001040113.1:c.5744A>C

Protein change:

D1908A

Molecular consequence:

NM_001143979.2:c.948-9219T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_017668.3:c.948-9219T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001040113.2:c.5744A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001040114.2:c.5744A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002474.3:c.5723A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_022844.3:c.5723A>C - 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
SCV004468838	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 6, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004468838

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 6, 2023)

germline

clinical testing

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

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

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, SCV004468838.1

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

Description

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) performed at Invitae indicates that this missense variant is not expected to disrupt MYH11 protein function. ClinVar contains an entry for this variant (Variation ID: 2442814). This variant has not been reported in the literature in individuals affected with MYH11-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 1915 of the MYH11 protein (p.Asp1915Ala).

#	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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