NM_000371.4(TTR):c.416C>T (p.Thr139Met) AND Amyloidosis, hereditary systemic 1

This record was updated by the submitter. Please see the current version.

Germline classification:: Benign/Likely benign (3 submissions)
Last evaluated:: Jan 29, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000990084.19

Allele description

NM_000371.4(TTR):c.416C>T (p.Thr139Met)

Gene:

TTR:transthyretin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_000371.4(TTR):c.416C>T (p.Thr139Met)

Other names:

T119M; p.T139M:ACG>ATG

HGVS:

NC_000018.10:g.31598647C>T
NG_009490.1:g.11881C>T
NM_000371.4:c.416C>TMANE SELECT
NP_000362.1:p.Thr139Met
NP_000362.1:p.Thr139Met
LRG_416t1:c.416C>T
LRG_416:g.11881C>T
LRG_416p1:p.Thr139Met
NC_000018.9:g.29178610C>T
NM_000371.3:c.416C>T
P02766:p.Thr139Met
c.416C>T

Protein change:

T139M; THR119MET

Links:

UniProtKB: P02766#VAR_007599; OMIM: 176300.0018; dbSNP: rs28933981

NCBI 1000 Genomes Browser:

rs28933981

Molecular consequence:

NM_000371.4:c.416C>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

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ubiquitin carboxyl-terminal hydrolase 20 [Mus musculus]
ubiquitin carboxyl-terminal hydrolase 20 [Mus musculus]
gi|30794162|ref|NP_083122.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000554851	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Jan 29, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001140875	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Likely benign (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV001284998	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Apr 27, 2017)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 1729893, 9090525, 1877623, 11577236, 1356051, 9395311 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000554851

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Benign
(Jan 29, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001140875

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2017)

Likely benign
(May 28, 2019)

unknown

clinical testing

Citation Link,

SCV001284998

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Benign
(Apr 27, 2017)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

From molecular variant to disease: initial steps in evaluating the association of transthyretin M119 with disease.

Ii S, Sobell JL, Sommer SS.

Am J Hum Genet. 1992 Jan;50(1):29-41.

PubMed [citation]

PMID:: 1729893
PMCID:: PMC1682512

See all PubMed Citations (7)

Details of each submission

From Invitae, SCV000554851.8

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

#	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

From Mendelics, SCV001140875.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Illumina Laboratory Services, Illumina, SCV001284998.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.

#	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 16, 2024

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