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NM_000371.4(TTR):c.418G>T (p.Ala140Ser) AND Cardiovascular phenotype

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jan 8, 2024
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:
RCV002327093.3

Allele description [Variation Report for NM_000371.4(TTR):c.418G>T (p.Ala140Ser)]

NM_000371.4(TTR):c.418G>T (p.Ala140Ser)

Gene:
TTR:transthyretin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
18q12.1
Genomic location:
Preferred name:
NM_000371.4(TTR):c.418G>T (p.Ala140Ser)
HGVS:
  • NC_000018.10:g.31598649G>T
  • NG_009490.1:g.11883G>T
  • NM_000371.4:c.418G>TMANE SELECT
  • NP_000362.1:p.Ala140Ser
  • NP_000362.1:p.Ala140Ser
  • LRG_416t1:c.418G>T
  • LRG_416:g.11883G>T
  • LRG_416p1:p.Ala140Ser
  • NC_000018.9:g.29178612G>T
  • NM_000371.3:c.418G>T
  • P02766:p.Ala140Ser
Protein change:
A140S
Links:
UniProtKB: P02766#VAR_038986; dbSNP: rs876658108
NCBI 1000 Genomes Browser:
rs876658108
Molecular consequence:
  • NM_000371.4:c.418G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV002630791Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)
Likely pathogenic
(Jan 8, 2024)
germlineclinical testing

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

Citation Link

Summary from all submissions

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

Citations

PubMed

Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis.

Lachmann HJ, Booth DR, Booth SE, Bybee A, Gilbertson JA, Gillmore JD, Pepys MB, Hawkins PN.

N Engl J Med. 2002 Jun 6;346(23):1786-91.

PubMed [citation]
PMID:
12050338

TTR-related amyloid neuropathy: clinical, electrophysiological and pathological findings in 15 unrelated patients.

Luigetti M, Conte A, Del Grande A, Bisogni G, Madia F, Lo Monaco M, Laurenti L, Obici L, Merlini G, Sabatelli M.

Neurol Sci. 2013 Jul;34(7):1057-63. doi: 10.1007/s10072-012-1105-y. Epub 2012 May 17.

PubMed [citation]
PMID:
22592564
See all PubMed Citations (7)

Details of each submission

From Ambry Genetics, SCV002630791.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

The p.A140S variant (also known as c.418G>T and p.A120S), located in coding exon 4 of the TTR gene, results from a G to T substitution at nucleotide position 418. The alanine at codon 140 is replaced by serine, an amino acid with similar properties. This variant, which is also known as p.A120S, has been reported in multiple individuals with transthyretin (TTR) amyloidosis (Gürsoy AE et al. Neurol India;66:238-241; Patel K et al. Amyloid, 2018 09;25:211-212; Iorio A et al. Eur J Hum Genet, 2017 09;25:1055-1060; Shibata Y et al. Amyloid, 2017 03;24:66-67; Luigetti M et al. Neurol Sci, 2013 Jul;34:1057-63; Lachmann HJ et al. N Engl J Med, 2002 Jun;346:1786-91; Adams D et al. Neurology, 2015 Aug;85:675-82). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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: Jun 17, 2024