NM_000371.4(TTR):c.128G>A (p.Ser43Asn) AND Familial amyloid neuropathy

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 31, 2022
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:: RCV000819070.17

Allele description [Variation Report for NM_000371.4(TTR):c.128G>A (p.Ser43Asn)]

NM_000371.4(TTR):c.128G>A (p.Ser43Asn)

Gene:

TTR:transthyretin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_000371.4(TTR):c.128G>A (p.Ser43Asn)

HGVS:

NC_000018.10:g.31592954G>A
NG_009490.1:g.6188G>A
NM_000371.4:c.128G>AMANE SELECT
NP_000362.1:p.Ser43Asn
NP_000362.1:p.Ser43Asn
LRG_416t1:c.128G>A
LRG_416:g.6188G>A
LRG_416p1:p.Ser43Asn
NC_000018.9:g.29172917G>A
NM_000371.3:c.128G>A

Protein change:

S43N

Links:

dbSNP: rs1598844112

NCBI 1000 Genomes Browser:

rs1598844112

Molecular consequence:

NM_000371.4:c.128G>A - missense variant - [Sequence Ontology: SO:0001583]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000959712	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 31, 2022)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 10439117, 22149423, 22400056, 23713495, 26428663, 28878402, 28492532
SCV002519917	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2019)	Pathogenic (May 4, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000959712

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 31, 2022)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

SCV002519917

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2019)

Pathogenic
(May 4, 2022)

germline

clinical testing

Citation Link

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

A new transthyretin variant (Ser23Asn) associated with familial amyloidosis in a Portuguese patient.

Connors LH, Théberge R, Skare J, Costello CE, Falk RH, Skinner M.

Amyloid. 1999 Jun;6(2):114-8.

PubMed [citation]

PMID:: 10439117

Technetium pyrophosphate myocardial uptake and peripheral neuropathy in a rare variant of familial transthyretin (TTR) amyloidosis (Ser23Asn): a case report and literature review.

Castaño A, Bokhari S, Brannagan TH 3rd, Wynn J, Maurer MS.

Amyloid. 2012 Mar;19(1):41-6. doi: 10.3109/13506129.2011.638682. Epub 2011 Dec 8. Review.

PubMed [citation]

PMID:: 22149423
PMCID:: PMC4934899

See all PubMed Citations (7)

Details of each submission

From Invitae, SCV000959712.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 43 of the TTR protein (p.Ser43Asn). 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: 661615). This variant is also known as p.Ser23Asn. This missense change has been observed in individual(s) with hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) (PMID: 10439117, 22149423, 22400056, 23713495, 26428663, 28878402). This variant is not present in population databases (gnomAD no frequency).

#	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, SCV002519917.1

#	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	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 29, 2024

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