NM_000371.4(TTR):c.161G>C (p.Arg54Thr) AND Amyloidosis, hereditary systemic 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 14, 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:: RCV001042832.6

Allele description [Variation Report for NM_000371.4(TTR):c.161G>C (p.Arg54Thr)]

NM_000371.4(TTR):c.161G>C (p.Arg54Thr)

Gene:

TTR:transthyretin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_000371.4(TTR):c.161G>C (p.Arg54Thr)

HGVS:

NC_000018.10:g.31592987G>C
NG_009490.1:g.6221G>C
NM_000371.4:c.161G>CMANE SELECT
NP_000362.1:p.Arg54Thr
LRG_416t1:c.161G>C
LRG_416:g.6221G>C
NC_000018.9:g.29172950G>C
NM_000371.3:c.161G>C

Protein change:

R54T

Links:

dbSNP: rs1598844187

NCBI 1000 Genomes Browser:

rs1598844187

Molecular consequence:

NM_000371.4:c.161G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Amyloidosis, hereditary systemic 1 (AMYLD1)
Synonyms:: Amyloidosis Transthyretin related; Amyloid polyneuropathy transthyretin related; Transthyretin amyloidosis; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0971004; MedGen: C2751492; Orphanet: 85447; Orphanet: 85451; OMIM: 105210

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001206537	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 14, 2021)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 9605286, 21692911, 22745357, 23713495, 22187309, 22973891, 17503405, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001206537

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 14, 2021)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

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

Novel transthyretin missense mutation (Thr34) in an Italian family with hereditary amyloidosis.

Patrosso MC, Salvi F, De Grandis D, Vezzoni P, Jacobson DR, Ferlini A.

Am J Med Genet. 1998 May 1;77(2):135-8.

PubMed [citation]

PMID:: 9605286

Variable presentations of TTR-related familial amyloid polyneuropathy in seventeen patients.

Cappellari M, Cavallaro T, Ferrarini M, Cabrini I, Taioli F, Ferrari S, Merlini G, Obici L, Briani C, Fabrizi GM.

J Peripher Nerv Syst. 2011 Jun;16(2):119-29. doi: 10.1111/j.1529-8027.2011.00331.x.

PubMed [citation]

PMID:: 21692911

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001206537.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This variant is also known as G1692C, Arg34Thr. This missense change has been observed in individual(s) with hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) (PMID: 9605286, 21692911, 22745357, 23713495). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with threonine at codon 54 of the TTR protein (p.Arg54Thr). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and threonine. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg54 amino acid residue in TTR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22187309, 22973891). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects TTR function (PMID: 17503405).

#	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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