NM_000371.4(TTR):c.171TGA[1] (p.Asp59del) AND Familial amyloid neuropathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 6, 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:: RCV000647357.5

Allele description [Variation Report for NM_000371.4(TTR):c.171TGA[1] (p.Asp59del)]

NM_000371.4(TTR):c.171TGA[1] (p.Asp59del)

Gene:

TTR:transthyretin [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_000371.4(TTR):c.171TGA[1] (p.Asp59del)

HGVS:

NC_000018.10:g.31592997TGA[1]
NG_009490.1:g.6231TGA[1]
NM_000371.4:c.171TGA[1]MANE SELECT
NP_000362.1:p.Asp59del
LRG_416:g.6231TGA[1]
NC_000018.9:g.29172960TGA[1]
NC_000018.9:g.29172960_29172962del
NM_000371.3:c.174_176delTGA

Protein change:

D59del

Links:

dbSNP: rs1555631238

NCBI 1000 Genomes Browser:

rs1555631238

Molecular consequence:

NM_000371.4:c.171TGA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:: Familial amyloid neuropathy (AMYLD1)
Synonyms:: Amyloidosis Transthyretin related; Amyloid polyneuropathy transthyretin related; Transthyretin amyloidosis; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007100; MedGen: C2751492; Orphanet: 85447; Orphanet: 85451; OMIM: 105210

Recent activity

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N-acetylglucosamine 6-phosphate deacetylase [Bacteroides helcogenes P 36-108]
N-acetylglucosamine 6-phosphate deacetylase [Bacteroides helcogenes P 36-108]
gi|319417537|gnl|jgi|Bache_2703|gb| 648.1|

Protein
txid2146041[Organism:noexp] (1)
Identical Protein Groups

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000769149	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 6, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25644864, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000769149

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 6, 2017)

germline

clinical testing

PubMed (2)
[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

Asp58Ala is the predominant mutation of the TTR gene in Korean patients with hereditary transthyretin-related amyloidosis.

Jang MA, Lee GY, Kim K, Kim SJ, Kim JS, Lee SY, Kim HJ, Jeon ES.

Ann Hum Genet. 2015 Mar;79(2):99-107. doi: 10.1111/ahg.12101. Epub 2015 Jan 23.

PubMed [citation]

PMID:: 25644864

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

Details of each submission

From Invitae, SCV000769149.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. It is not possible to discern whether this amino acid deletion affects codon 58 or 59 since the same sequence is present at both positions with two consecutive aspartic acid amino acids. A missense substitution at codon 59 (p.Asp59Ala) has been determined to be pathogenic (PMID: 25644864). This suggests that the asparagine residue is critical for TTR protein function and that other missense substitutions or deletions at this position may also be pathogenic. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid is currently unknown. This variant has not been reported in the literature in individuals with TTR-related disease. This variant is not present in population databases (ExAC no frequency). This variant, c.174_176delTGA, results in the deletion of 1 amino acid of the TTR protein (p.Asp59del), but otherwise preserves the integrity of the reading frame.

#	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: Jun 17, 2024

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