NM_000371.4(TTR):c.155T>C (p.Val52Ala) AND Cardiovascular phenotype

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 24, 2021
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:: RCV002402641.2

Allele description [Variation Report for NM_000371.4(TTR):c.155T>C (p.Val52Ala)]

NM_000371.4(TTR):c.155T>C (p.Val52Ala)

Gene:

TTR:transthyretin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_000371.4(TTR):c.155T>C (p.Val52Ala)

HGVS:

NC_000018.10:g.31592981T>C
NG_009490.1:g.6215T>C
NM_000371.4:c.155T>CMANE SELECT
NP_000362.1:p.Val52Ala
LRG_416t1:c.155T>C
LRG_416:g.6215T>C
NC_000018.9:g.29172944T>C
NM_000371.3:c.155T>C

Protein change:

V52A

Links:

dbSNP: rs2073493951

NCBI 1000 Genomes Browser:

rs2073493951

Molecular consequence:

NM_000371.4:c.155T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Ovis aries strain OAR_USU_Benz2616 breed Rambouillet chromosome 8, ARS-UI_Ramb_v...
Ovis aries strain OAR_USU_Benz2616 breed Rambouillet chromosome 8, ARS-UI_Ramb_v3.0, whole genome shotgun sequence
gi|2055116845|gnl|ASM:GCF_016772055 fold_chr8|ref|NC_056061.1||gpp|GPC_000010596.1||gnl|NCBI_GENOMES|107614

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002708886	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Aug 24, 2021)	germline	clinical testing	PubMed (12) [See all records that cite these PMIDs] 14627687, 15793844, 17484624, 19467548, 20937937, 23240369, 24101130, 26656838, 29524093, 30685801, 33114611, 8536704 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002708886

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Aug 24, 2021)

germline

clinical testing

PubMed (12)
[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

A novel transthyretin mutation V32A in a Chinese man with late-onset amyloid polyneuropathy.

Pica EC, Pramono ZA, Verma KK, San LP, Chee YW.

Muscle Nerve. 2005 Aug;32(2):223-5.

PubMed [citation]

PMID:: 15793844

See all PubMed Citations (12)

Details of each submission

From Ambry Genetics, SCV002708886.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (12)

Description

The p.V52A variant (also known as c.155T>C and V32A), located in coding exon 2 of the TTR gene, results from a T to C substitution at nucleotide position 155. The valine at codon 52 is replaced by alanine, an amino acid with similar properties. This alteration has been reported in an individual with confirmed amyloid polyneuropathy and in additional polyneuropathy cases (Pica EC et al. Muscle Nerve, 2005 Aug;32:223-5; Kaplan B et al. Clin. Chem. Lab. Med., 2007;45:625-8; Luigetti M et al. Brain Sci, 2020 Oct;10:[Epub ahead of print]). A different variant at this same amino acid position, p.V52G, has also been reported in a family with amyloid neuropathy (Planté-Bordeneuve V et al. J. Med. Genet., 2003 Nov;40:e120). Based on internal structural assessment, this alteration destabilizes the structure of TTR (Ambry internal data; Zanotti G et al. Eur. J. Biochem., 1995 Dec;234:563-9). 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: Sep 29, 2024

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