NM_000371.4(TTR):c.116C>A (p.Ala39Asp) AND Cardiovascular phenotype

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

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 18, 2022
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:: RCV002331319.2

Allele description

NM_000371.4(TTR):c.116C>A (p.Ala39Asp)

Gene:

TTR:transthyretin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_000371.4(TTR):c.116C>A (p.Ala39Asp)

HGVS:

NC_000018.10:g.31592942C>A
NG_009490.1:g.6176C>A
NM_000371.4:c.116C>AMANE SELECT
NP_000362.1:p.Ala39Asp
NP_000362.1:p.Ala39Asp
LRG_416t1:c.116C>A
LRG_416:g.6176C>A
LRG_416p1:p.Ala39Asp
NC_000018.9:g.29172905C>A
NM_000371.3:c.116C>A

Protein change:

A39D

Links:

dbSNP: rs11541795

NCBI 1000 Genomes Browser:

rs11541795

Molecular consequence:

NM_000371.4:c.116C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002631660	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Likely pathogenic (Nov 18, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 22106346, 24358189, 26537620, 31648569 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002631660

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Likely pathogenic
(Nov 18, 2022)

germline

clinical testing

PubMed (4)
[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

Immunohistochemistry in the classification of systemic forms of amyloidosis: a systematic investigation of 117 patients.

Schönland SO, Hegenbart U, Bochtler T, Mangatter A, Hansberg M, Ho AD, Lohse P, Röcken C.

Blood. 2012 Jan 12;119(2):488-93. doi: 10.1182/blood-2011-06-358507. Epub 2011 Nov 21.

PubMed [citation]

PMID:: 22106346

Structure-based analysis of A19D, a variant of transthyretin involved in familial amyloid cardiomyopathy.

Ferreira P, Sant'Anna R, Varejão N, Lima C, Novis S, Barbosa RV, Caldeira CM, Rumjanek FD, Ventura S, Cruz MW, Foguel D.

PLoS One. 2013;8(12):e82484. doi: 10.1371/journal.pone.0082484. Erratum in: PLoS One. 2013;8(12). doi:10.1371/annotation/2ea264c2-d70c-4a2e-b877-c084dc3a49db. Sant'Anna, Oliveira [corrected to Sant'Anna, Ricardo].

PubMed [citation]

PMID:: 24358189
PMCID:: PMC3866121

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV002631660.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The p.A39D variant (also known as c.116C>A), located in coding exon 2 of the TTR gene, results from a C to A substitution at nucleotide position 116. The alanine at codon 39 is replaced by aspartic acid, an amino acid with dissimilar properties. This alteration, which is also known as p.A19D, has been reported in individuals with transthyretin (TTR) amyloidosis who had neuropathy and cardiac involvement (Schönland SO et al. Blood, 2012 Jan;119:488-93; Ferreira P et al. PLoS ONE, 2013 Dec;8:e82484; Damy T et al. Eur Heart J, 2016 06;37:1826-34; Niemietz C et al. Amyloid, 2020 Mar;27:45-51). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. 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: Apr 15, 2024

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