NM_014391.3(ANKRD1):c.368C>T (p.Thr123Met) AND ANKRD1-related dilated cardiomyopathy

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 30, 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:: RCV000458316.9

Allele description

NM_014391.3(ANKRD1):c.368C>T (p.Thr123Met)

Gene:

ANKRD1:ankyrin repeat domain 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q23.31

Genomic location:

Preferred name:

NM_014391.3(ANKRD1):c.368C>T (p.Thr123Met)

Other names:

p.T123M:ACG>ATG

HGVS:

NC_000010.11:g.90918950G>A
NG_023227.1:g.7326C>T
NM_014391.3:c.368C>TMANE SELECT
NP_055206.2:p.Thr123Met
NP_055206.2:p.Thr123Met
LRG_379t1:c.368C>T
LRG_379:g.7326C>T
LRG_379p1:p.Thr123Met
NC_000010.10:g.92678707G>A
NM_014391.2:c.368C>T

Protein change:

T123M

Links:

dbSNP: rs145387010

NCBI 1000 Genomes Browser:

rs145387010

Molecular consequence:

NM_014391.3:c.368C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: ANKRD1-related dilated cardiomyopathy
Identifiers:: MedGen: CN119551

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000553446	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 30, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19608031, 31737537, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000553446

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 30, 2023)

germline

clinical testing

PubMed (3)
[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

Cardiac ankyrin repeat protein gene (ANKRD1) mutations in hypertrophic cardiomyopathy.

Arimura T, Bos JM, Sato A, Kubo T, Okamoto H, Nishi H, Harada H, Koga Y, Moulik M, Doi YL, Towbin JA, Ackerman MJ, Kimura A.

J Am Coll Cardiol. 2009 Jul 21;54(4):334-42. doi: 10.1016/j.jacc.2008.12.082.

PubMed [citation]

PMID:: 19608031

Variant panorama in 1,385 index patients and sensitivity of expanded next-generation sequencing panels in arrhythmogenic disorders.

Marschall C, Moscu-Gregor A, Klein HG.

Cardiovasc Diagn Ther. 2019 Oct;9(Suppl 2):S292-S298. doi: 10.21037/cdt.2019.06.06.

PubMed [citation]

PMID:: 31737537
PMCID:: PMC6837920

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000553446.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 123 of the ANKRD1 protein (p.Thr123Met). This variant is present in population databases (rs145387010, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 19608031, 31737537). ClinVar contains an entry for this variant (Variation ID: 191577). 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 ANKRD1 protein function with a negative predictive value of 80%. 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: May 19, 2024

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