NM_000371.4(TTR):c.140A>G (p.Asn47Ser) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 12, 2020
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:: RCV000766992.6

Allele description [Variation Report for NM_000371.4(TTR):c.140A>G (p.Asn47Ser)]

NM_000371.4(TTR):c.140A>G (p.Asn47Ser)

Gene:

TTR:transthyretin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_000371.4(TTR):c.140A>G (p.Asn47Ser)

Other names:

p.N47S:AAT>AGT

HGVS:

NC_000018.10:g.31592966A>G
NG_009490.1:g.6200A>G
NM_000371.4:c.140A>GMANE SELECT
NP_000362.1:p.Asn47Ser
NP_000362.1:p.Asn47Ser
LRG_416t1:c.140A>G
LRG_416:g.6200A>G
LRG_416p1:p.Asn47Ser
NC_000018.9:g.29172929A>G
NM_000371.3:c.140A>G

Protein change:

N47S

Links:

dbSNP: rs145551875

NCBI 1000 Genomes Browser:

rs145551875

Molecular consequence:

NM_000371.4:c.140A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000209368	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Apr 29, 2015)	germline	clinical testing	Citation Link,
SCV001715215	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 12, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000209368

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Apr 29, 2015)

germline

clinical testing

Citation Link,

SCV001715215

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Feb 12, 2020)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV000209368.13

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

Description

This variant is denoted p.Asn47Ser (AAT>AGT): c.140 A>G in exon 2 of the TTR gene (NM_000371.3). The N47S variant in the TTR gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. N47S was not observed with any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Mutations in nearby residues (A45T, V48M) have been reported in association with TTR-related amyloidosis, supporting the functional importance of this region of the protein. However, N47S is only a conservative amino acid substitution as these residues share similar properties, and are least likely to impact secondary structure. In addition, the N47 residue is not well conserved across species, and in silico analysis predicts N47S is benign to the protein structure/function. With the clinical and molecular information available at this time, we cannot definitively determine if N47S is a disease-causing mutation or a rare benign variant. The variant is found in DCM-CRDM panel(s).

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

From Mayo Clinic Laboratories, Mayo Clinic, SCV001715215.1

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

Last Updated: Sep 29, 2024

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