VCV000374963.23 - ClinVar

NM_002474.3(MYH11):c.5732C>T (p.Thr1911Met)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(8)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Conflicting classifications of pathogenicity
Uncertain significance(2); Likely benign(4)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_002474.3(MYH11):c.5732C>T (p.Thr1911Met)

Variation ID: 374963 Accession: VCV000374963.23

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 16p13.11 16: 15714963 (GRCh38) [ NCBI UCSC ] 16: 15808820 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jan 23, 2017	Oct 20, 2024	May 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_002474.3:c.5732C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_002465.1:p.Thr1911Met	missense
NM_017668.3:c.948-9228G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_001040113.2:c.5753C>T MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001035202.1:p.Thr1918Met	missense
NM_001040114.2:c.5753C>T	NP_001035203.1:p.Thr1918Met	missense
NM_001143979.2:c.948-9228G>A		intron variant
NM_022844.3:c.5732C>T	NP_074035.1:p.Thr1911Met	missense
NC_000016.10:g.15714963G>A
NC_000016.9:g.15808820G>A
NG_009299.1:g.147068C>T
NG_021210.1:g.76697G>A
LRG_1401:g.147068C>T
LRG_1401t1:c.5732C>T	LRG_1401p1:p.Thr1911Met
LRG_1401t2:c.5753C>T	LRG_1401p2:p.Thr1918Met

... more HGVS ... less HGVS

Protein change

T1918M, T1911M

Other names

Canonical SPDI

NC_000016.10:15714962:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD) 0.00008

Trans-Omics for Precision Medicine (TOPMed) 0.00008

Exome Aggregation Consortium (ExAC) 0.00013

The Genome Aggregation Database (gnomAD), exomes 0.00017

Links

ClinGen: CA7921155 dbSNP: rs748516947 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
MYH11		No evidence available	No evidence available	GRCh38 GRCh38 GRCh37	2037	3810
NDE1		-	-	GRCh38 GRCh38 GRCh37	186	1959

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Aortic aneurysm, familial thoracic 4	Conflicting interpretations of pathogenicity (3)	criteria provided, conflicting classifications	Jan 24, 2024	RCV000415719.14
Familial thoracic aortic aneurysm and aortic dissection	Likely benign (1)	criteria provided, single submitter	Jun 11, 2018	RCV000772071.2
Isolated thoracic aortic aneurysm	Uncertain significance (1)	criteria provided, single submitter	Sep 1, 2018	RCV001374827.1
not provided	Likely benign (2)	criteria provided, multiple submitters, no conflicts	May 1, 2024	RCV001555668.7
MYH11-related disorder	Likely benign (1)	no assertion criteria provided	Aug 7, 2024	RCV004751513.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain significance (Oct 31, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Aortic aneurysm, familial thoracic 4 Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV000894981.1 First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019	Publications: PubMed (1) PubMed: 25741868 pmc: 4544753 pmc: 4544753 DOI: 10.1038/gim.2015.30 DOI: 10.1038/gim.2015.30
Likely benign (Jun 11, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Familial thoracic aortic aneurysm and aortic dissection Affected status: unknown Allele origin: germline	Color Diagnostics, LLC DBA Color Health Accession: SCV000905100.1 First in ClinVar: May 20, 2019 Last updated: May 20, 2019
Uncertain significance (Sep 01, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Isolated thoracic aortic aneurysm Affected status: yes Allele origin: germline	Department of Vascular Biology, Beijing Anzhen Hospital Accession: SCV001439576.1 First in ClinVar: Apr 28, 2021 Last updated: Apr 28, 2021	Sex: mixed
Likely benign (Sep 10, 2018)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001777120.1 First in ClinVar: Aug 13, 2021 Last updated: Aug 13, 2021
Likely benign (Jan 24, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Aortic aneurysm, familial thoracic 4 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000543706.8 First in ClinVar: Jan 23, 2017 Last updated: Feb 14, 2024
Likely benign (May 01, 2024)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV005051352.5 First in ClinVar: Jun 17, 2024 Last updated: Oct 20, 2024	Comment: MYH11: BS1 Number of individuals with the variant: 1
Uncertain significance (Mar 30, 2016)	no assertion criteria provided (ACMG Guidelines, 2015) Method: clinical testing	Aortic aneurysm, familial thoracic 4 Affected status: no Allele origin: germline	Knight Diagnostic Laboratories, Oregon Health and Sciences University Study: CSER-NextGen Accession: SCV000493768.1 First in ClinVar: Jan 23, 2017 Last updated: Jan 23, 2017
Likely benign (Aug 07, 2024)	no assertion criteria provided Method: clinical testing	MYH11-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV005365381.1 First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs748516947 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 20, 2024

ClinVar Genomic variation as it relates to human health

NM_002474.3(MYH11):c.5732C>T (p.Thr1911Met)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs748516947 ...