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NM_000371.4(TTR):c.130C>T (p.Pro44Ser) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 9, 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:
RCV002381523.2

Allele description [Variation Report for NM_000371.4(TTR):c.130C>T (p.Pro44Ser)]

NM_000371.4(TTR):c.130C>T (p.Pro44Ser)

Gene:
TTR:transthyretin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
18q12.1
Genomic location:
Preferred name:
NM_000371.4(TTR):c.130C>T (p.Pro44Ser)
Other names:
p.P44S:CCT>TCT
HGVS:
  • NC_000018.10:g.31592956C>T
  • NG_009490.1:g.6190C>T
  • NM_000371.4:c.130C>TMANE SELECT
  • NP_000362.1:p.Pro44Ser
  • NP_000362.1:p.Pro44Ser
  • LRG_416t1:c.130C>T
  • LRG_416:g.6190C>T
  • LRG_416p1:p.Pro44Ser
  • NC_000018.9:g.29172919C>T
  • NM_000371.3:c.130C>T
  • P02766:p.Pro44Ser
Protein change:
P44S
Links:
UniProtKB: P02766#VAR_007551; dbSNP: rs11541790
NCBI 1000 Genomes Browser:
rs11541790
Molecular consequence:
  • NM_000371.4:c.130C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002694312Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Oct 9, 2019) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Genetic microheterogeneity of human transthyretin detected by IEF.

Altland K, Benson MD, Costello CE, Ferlini A, Hazenberg BP, Hund E, Kristen AV, Linke RP, Merlini G, Salvi F, Saraiva MJ, Singer R, Skinner M, Winter P.

Electrophoresis. 2007 Jun;28(12):2053-64.

PubMed [citation]
PMID:
17503405

Clinical proteome informatics workbench detects pathogenic mutations in hereditary amyloidoses.

Dasari S, Theis JD, Vrana JA, Zenka RM, Zimmermann MT, Kocher JP, Highsmith WE Jr, Kurtin PJ, Dogan A.

J Proteome Res. 2014 May 2;13(5):2352-8. doi: 10.1021/pr4011475. Epub 2014 Apr 3.

PubMed [citation]
PMID:
24650283
See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV002694312.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

The p.P44S pathogenic mutation (also known as c.130C>T and p.P24S), located in coding exon 2 of the TTR gene, results from a C to T substitution at nucleotide position 130. The proline at codon 44 is replaced by serine, an amino acid with similar properties. This alteration was described in a 67-year-old individual with amyloid cardiomyopathy, bilateral carpal tunnel, and paresthesias of the lower limbs. Three additional affected family members and four asymptomatic family members also carried this alteration (Uemichi T et al. J. Med. Genet., 1995 Apr;32:279-81). This alteration was also detected in multiple individuals from a hereditary amyloidosis cohort (Dasari S et al. J. Proteome Res., 2014 May;13:2352-8; Koike H et al. J. Neurol. Sci., 2018 11;394:99-106). Electrophoretic analysis suggested that this alteration caused instability of the functional tetramer (Altland K et al. Electrophoresis, 2007 Jun;28:2053-64). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Feb 25, 2025