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NM_000371.4(TTR):c.239C>T (p.Thr80Ile) AND Cardiovascular phenotype

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Dec 13, 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:
RCV002458280.9

Allele description [Variation Report for NM_000371.4(TTR):c.239C>T (p.Thr80Ile)]

NM_000371.4(TTR):c.239C>T (p.Thr80Ile)

Gene:
TTR:transthyretin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
18q12.1
Genomic location:
Preferred name:
NM_000371.4(TTR):c.239C>T (p.Thr80Ile)
HGVS:
  • NC_000018.10:g.31595158C>T
  • NG_009490.1:g.8392C>T
  • NM_000371.4:c.239C>TMANE SELECT
  • NP_000362.1:p.Thr80Ile
  • NP_000362.1:p.Thr80Ile
  • LRG_416t1:c.239C>T
  • LRG_416:g.8392C>T
  • LRG_416p1:p.Thr80Ile
  • NC_000018.9:g.29175121C>T
  • NM_000371.3:c.239C>T
Protein change:
T80I
Links:
dbSNP: rs1254341785
NCBI 1000 Genomes Browser:
rs1254341785
Molecular consequence:
  • NM_000371.4:c.239C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002738512Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Dec 13, 2023) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Established and candidate transthyretin amyloidosis variants identified in the Saudi population by data mining.

Abouelhoda M, Mohty D, Alayary I, Meyer BF, Arold ST, Fadel BM, Monies D.

Hum Genomics. 2021 Aug 11;15(1):52. doi: 10.1186/s40246-021-00351-2.

PubMed [citation]
PMID:
34380564
PMCID:
PMC8359098

Genotype-Phenotype Correlation of a Rare Transthyretin Variant Causing Amyloidosis.

Chaudhary AG, AlReefi FM, Abou Zahr RG, Elzeftawy HA, Alghamdi SS, Bushnag AA, Al-Maghrabi JA, Abumansour IS.

CJC Open. 2022 Dec;4(12):1031-1035. doi: 10.1016/j.cjco.2022.09.005.

PubMed [citation]
PMID:
36562013
PMCID:
PMC9764124

Details of each submission

From Ambry Genetics, SCV002738512.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The p.T80I variant (also known as c.239C>T), located in coding exon 3 of the TTR gene, results from a C to T substitution at nucleotide position 239. The threonine at codon 80 is replaced by isoleucine, an amino acid with similar properties. This alteration has been reported in multiple patients with transthyretin (ATTR) amyloidosis (Ambry internal data; external communication; Chaudhary AG et al. CJC Open, 2022 Dec;4:1031-1035). This variant was also described in a Saudi exome cohort; however, clinical details were limited (Abouelhoda M et al. Hum Genomics, 2021 Aug;15:52). An alternate amino acid substitution at this position, p.T80A (historically described as p.T60A), has been detected in numerous individuals with ATTR amyloidosis and is associated with cardiac symptoms (Wallace MR et al. J. Clin. Invest., 1986 Jul;78:6-12; Zeldenrust SR. Amyloid, 2012 Jun;19 Suppl 1:22-4; Ihse E et al. Amyloid, 2013 Sep;20:142-50; Swiecicki PL et al. Amyloid, 2015 May;22:123-31). This variant was not reported in population-based 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 10, 2024