NM_002474.3(MYH11):c.12G>A (p.Lys4=) AND Aortic aneurysm, familial thoracic 4

Germline classification:: Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:: Jan 31, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000466346.31

Allele description [Variation Report for NM_002474.3(MYH11):c.12G>A (p.Lys4=)]

NM_002474.3(MYH11):c.12G>A (p.Lys4=)

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.12G>A (p.Lys4=)

Other names:

p.K4K:AAG>AAA

HGVS:

NC_000016.10:g.15838241C>T
NG_009299.1:g.23790G>A
NM_001040113.2:c.12G>A
NM_001040114.2:c.12G>A
NM_002474.3:c.12G>AMANE SELECT
NM_022844.3:c.12G>A
NP_001035202.1:p.Lys4=
NP_001035203.1:p.Lys4=
NP_002465.1:p.Lys4=
NP_074035.1:p.Lys4=
LRG_1401t1:c.12G>A
LRG_1401t2:c.12G>A
LRG_1401:g.23790G>A
LRG_1401p1:p.Lys4=
LRG_1401p2:p.Lys4=
NC_000016.9:g.15932098C>T
NM_001040113.1:c.12G>A
NM_002474.2:c.12G>A

Links:

dbSNP: rs112650390

NCBI 1000 Genomes Browser:

rs112650390

Molecular consequence:

NM_001040113.2:c.12G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001040114.2:c.12G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_002474.3:c.12G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_022844.3:c.12G>A - synonymous variant - [Sequence Ontology: SO:0001819]

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
SCV000556114	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Jan 31, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000745491	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus	criteria provided, single submitter (ACGS Guidelines, 2013)	Likely benign (Jun 28, 2017)	germline	clinical testing	Citation Link,
SCV000745980	Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus	no assertion criteria provided (ACGS Guidelines, 2013)	Likely benign (Mar 23, 2015)	germline	clinical testing	Citation Link,
SCV001274988	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Jan 12, 2018)	germline	clinical testing	Citation Link

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
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, SCV000556114.9

#	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 Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV000745491.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus, SCV000745980.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Illumina Laboratory Services, Illumina, SCV001274988.1

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

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

#	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: Nov 24, 2024

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