NM_000371.4(TTR):c.182G>T (p.Trp61Leu) AND Amyloidosis, hereditary systemic 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 10, 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:: RCV001389003.6

Allele description [Variation Report for NM_000371.4(TTR):c.182G>T (p.Trp61Leu)]

NM_000371.4(TTR):c.182G>T (p.Trp61Leu)

Gene:

TTR:transthyretin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_000371.4(TTR):c.182G>T (p.Trp61Leu)

HGVS:

NC_000018.10:g.31593008G>T
NG_009490.1:g.6242G>T
NM_000371.4:c.182G>TMANE SELECT
NP_000362.1:p.Trp61Leu
LRG_416:g.6242G>T
NC_000018.9:g.29172971G>T

Protein change:

W61L

Links:

dbSNP: rs1567945702

NCBI 1000 Genomes Browser:

rs1567945702

Molecular consequence:

NM_000371.4:c.182G>T - 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

Recent activity

Clear Turn Off Turn On

Ventricular tachycardia, somatic
Ventricular tachycardia, somatic

MedGen
C4016143[conceptid] (1)
MedGen

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001590204	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 10, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12557756, 26959691, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001590204

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 10, 2023)

germline

clinical testing

PubMed (3)
[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

Transthyretin amyloidosis associated with a novel variant (Trp41Leu) presenting with vitreous opacities.

Yazaki M, Connors LH, Eagle RC Jr, Leff SR, Skinner M, Benson MD.

Amyloid. 2002 Dec;9(4):263-7.

PubMed [citation]

PMID:: 12557756

Cutaneous Manifestations of Familial Transthyretin Amyloid Polyneuropathy.

Lanoue J, Wei N, Gorevic P, Phelps RG.

Am J Dermatopathol. 2016 Oct;38(10):719-25. doi: 10.1097/DAD.0000000000000501. Review.

PubMed [citation]

PMID:: 26959691

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001590204.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TTR protein function. ClinVar contains an entry for this variant (Variation ID: 1075408). This variant is also known as p.Trp41Leu. This missense change has been observed in individual(s) with hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) (PMID: 12557756, 26959691). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tryptophan, which is neutral and slightly polar, with leucine, which is neutral and non-polar, at codon 61 of the TTR protein (p.Trp61Leu).

#	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

ClinVar

Relating variation to medicine