NM_002474.3(MYH11):c.1990C>G (p.Leu664Val) AND Aortic aneurysm, familial thoracic 4

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 1, 2021
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:: RCV000536873.5

Allele description

NM_002474.3(MYH11):c.1990C>G (p.Leu664Val)

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.1990C>G (p.Leu664Val)

HGVS:

NC_000016.10:g.15750206G>C
NG_009299.1:g.111825C>G
NM_001040113.2:c.2011C>G
NM_001040114.2:c.2011C>G
NM_002474.3:c.1990C>GMANE SELECT
NM_022844.3:c.1990C>G
NP_001035202.1:p.Leu671Val
NP_001035203.1:p.Leu671Val
NP_002465.1:p.Leu664Val
NP_074035.1:p.Leu664Val
LRG_1401t1:c.1990C>G
LRG_1401t2:c.2011C>G
LRG_1401:g.111825C>G
LRG_1401p1:p.Leu664Val
LRG_1401p2:p.Leu671Val
NC_000016.9:g.15844063G>C
NM_001040113.1:c.2011C>G

Protein change:

L664V

Links:

dbSNP: rs762549707

NCBI 1000 Genomes Browser:

rs762549707

Molecular consequence:

NM_001040113.2:c.2011C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001040114.2:c.2011C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_002474.3:c.1990C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_022844.3:c.1990C>G - 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
SCV000641005	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 1, 2021)	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

SCV000641005

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 1, 2021)

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 Invitae, SCV000641005.3

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

Description

This sequence change replaces leucine with valine at codon 671 of the MYH11 protein (p.Leu671Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs762549707, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with MYH11-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.

#	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: Feb 20, 2024

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