NM_000371.4(TTR):c.206C>G (p.Thr69Ser) AND Familial amyloid neuropathy

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 10, 2017
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:: RCV000647353.5

Allele description [Variation Report for NM_000371.4(TTR):c.206C>G (p.Thr69Ser)]

NM_000371.4(TTR):c.206C>G (p.Thr69Ser)

Gene:

TTR:transthyretin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_000371.4(TTR):c.206C>G (p.Thr69Ser)

HGVS:

NC_000018.10:g.31595125C>G
NG_009490.1:g.8359C>G
NM_000371.4:c.206C>GMANE SELECT
NP_000362.1:p.Thr69Ser
NP_000362.1:p.Thr69Ser
LRG_416t1:c.206C>G
LRG_416:g.8359C>G
LRG_416p1:p.Thr69Ser
NC_000018.9:g.29175088C>G
NM_000371.3:c.206C>G

Protein change:

T69S

Links:

dbSNP: rs1555631387

NCBI 1000 Genomes Browser:

rs1555631387

Molecular consequence:

NM_000371.4:c.206C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial amyloid neuropathy
Synonyms:: Amyloidosis Transthyretin related; Amyloid polyneuropathy transthyretin related; TTR amyloid neuropathy; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007100; 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
SCV000769144	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Oct 10, 2017)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 25044787, 26115788, 1301926, 17503405, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000769144

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Oct 10, 2017)

germline

clinical testing

PubMed (5)
[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

Online registry for mutations in hereditary amyloidosis including nomenclature recommendations.

Rowczenio DM, Noor I, Gillmore JD, Lachmann HJ, Whelan C, Hawkins PN, Obici L, Westermark P, Grateau G, Wechalekar AD.

Hum Mutat. 2014 Sep;35(9):E2403-12. doi: 10.1002/humu.22619. Epub 2014 Aug 4.

PubMed [citation]

PMID:: 25044787

Three Turkish families with different transthyretin mutations.

Bekircan-Kurt CE, Güneş N, Yılmaz A, Erdem-Özdamar S, Tan E.

Neuromuscul Disord. 2015 Sep;25(9):686-92. doi: 10.1016/j.nmd.2015.05.010. Epub 2015 May 27.

PubMed [citation]

PMID:: 26115788

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000769144.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C55"). This variant has been reported in several individuals affected with hereditary amyloidosis (PMID: 25044787, 26115788, Invitae). This variant is also known as p.Thr49Ser in the literature. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with serine at codon 69 of the TTR protein (p.Thr69Ser). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and serine. A different missense substitution at this codon (p.Thr69Ala) has been determined to be pathogenic (PMID: 1301926, 17503405, 20209591, 23713495, 21692911, 27859927). This suggests that the threonine residue is critical for TTR protein function and that other missense substitutions at this position may also be pathogenic. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#	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: Apr 15, 2024

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