NM_000371.4(TTR):c.241G>A (p.Glu81Lys) AND Cardiovascular phenotype

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 30, 2019
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:: RCV002453259.2

Allele description [Variation Report for NM_000371.4(TTR):c.241G>A (p.Glu81Lys)]

NM_000371.4(TTR):c.241G>A (p.Glu81Lys)

Gene:

TTR:transthyretin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_000371.4(TTR):c.241G>A (p.Glu81Lys)

Other names:

E61K

HGVS:

NC_000018.10:g.31595160G>A
NG_009490.1:g.8394G>A
NM_000371.4:c.241G>AMANE SELECT
NP_000362.1:p.Glu81Lys
LRG_416t1:c.241G>A
LRG_416:g.8394G>A
NC_000018.9:g.29175123G>A
NM_000371.3:c.241G>A
P02766:p.Glu81Lys

Protein change:

E81K; GLU61LYS

Links:

UniProtKB: P02766#VAR_007574; OMIM: 176300.0031; dbSNP: rs121918086

NCBI 1000 Genomes Browser:

rs121918086

Molecular consequence:

NM_000371.4:c.241G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002736015	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Jan 30, 2019)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 14627687, 20536403, 25130926, 28991715, 29801893, 29883834, 8352764 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002736015

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Jan 30, 2019)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

Citation Link

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

Genetic study of transthyretin amyloid neuropathies: carrier risks among French and Portuguese families.

Planté-Bordeneuve V, Carayol J, Ferreira A, Adams D, Clerget-Darpoux F, Misrahi M, Said G, Bonaïti-Pellié C.

J Med Genet. 2003 Nov;40(11):e120. No abstract available.

PubMed [citation]

PMID:: 14627687
PMCID:: PMC1735318

Cardiomyopathy in a Japanese family with the Glu61Lys transthyretin variant: a new phenotype.

Noto Y, Tokuda T, Shiga K, Tsuchiya A, Yazaki M, Matoba S, Nakagawa M.

Amyloid. 2009;16(2):99-102. doi: 10.1080/13506120902879335.

PubMed [citation]

PMID:: 20536403

See all PubMed Citations (7)

Details of each submission

From Ambry Genetics, SCV002736015.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

The p.E81K variant (also known as c.241G>A), located in coding exon 3 of the TTR gene, results from a G to A substitution at nucleotide position 241. The glutamic acid at codon 81 is replaced by lysine, an amino acid with similar properties. This variant (also referred to as Glu61lys) has been reported in TTR amyloidosis cohorts and in individuals reported to have transthyretin amyloidosis characterized by later onset sensory-autonomic polyneuropathy and cardiomyopathy (Planté-Bordeneuve V et al. J. Med. Genet., 2003 Nov;40:e120; Noto Y et al. Amyloid, 2009;16:99-102; Hagenacker T et al. J. Neurol. Sci., 2014 Nov;346:331-2; Murakami T et al. J. Neurol. Sci., 2017 Oct;381:55-58; Nakano Y et al. J. Neurol. Sci., 2018 Jul;390:22-25). In addition, another variant affecting this codon (p.E81G, c.242A>G and referred to as Glu61Gly) has also been reported in an individual with transthyretin amyloidosis (Rosenzweig M et al. Amyloid, 2007 Mar;14:65-71). In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#	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: Jun 17, 2024

ClinVar

Relating variation to medicine