NM_000371.4(TTR):c.424G>A (p.Val142Ile) AND Amyloid Cardiomyopathy, Transthyretin-related

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 18, 2011
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:: RCV000030575.10

Allele description [Variation Report for NM_000371.4(TTR):c.424G>A (p.Val142Ile)]

NM_000371.4(TTR):c.424G>A (p.Val142Ile)

Gene:

TTR:transthyretin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_000371.4(TTR):c.424G>A (p.Val142Ile)

Other names:

V122I; p.V142I:GTC>ATC

HGVS:

NC_000018.10:g.31598655G>A
NG_009490.1:g.11889G>A
NM_000371.4:c.424G>AMANE SELECT
NP_000362.1:p.Val142Ile
NP_000362.1:p.Val142Ile
LRG_416t1:c.424G>A
LRG_416:g.11889G>A
LRG_416p1:p.Val142Ile
NC_000018.9:g.29178618G>A
NM_000371.3:c.424G>A
P02766:p.Val142Ile
c.424G>A
p.V122I
p.VAL142ILE

Protein change:

V142I; VAL122ILE

Links:

UniProtKB: P02766#VAR_007600; OMIM: 176300.0009; dbSNP: rs76992529

NCBI 1000 Genomes Browser:

rs76992529

Molecular consequence:

NM_000371.4:c.424G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Amyloid Cardiomyopathy, Transthyretin-related (ICA)
Synonyms:: Isolated Cardiac Amyloidosis
Identifiers:: MedGen: C3151471

Recent activity

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alpha-D-glucose phosphate-specific phosphoglucomutase [Aquiluna borgnonia]
alpha-D-glucose phosphate-specific phosphoglucomutase [Aquiluna borgnonia]
gi|1850313682|gnl|PRJNA510297|HRU87 0|gb|QKJ25841.1|

Protein
LOC100131680 [Homo sapiens]
LOC100131680 [Homo sapiens]
Gene ID:100131680

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000053250	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	pathogenic (Aug 18, 2011)	germline	curation, clinical testing	PubMed (18) [See all records that cite these PMIDs] 17503405, 2237288, 11752443, 12874413, 16631014, 16631015, 18318779, 18830126, 16432141, 2590199, 1997217, 19781421, 12874414, 10762172, 14569203, 12217248, 10842715, 15123043 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000053250

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

pathogenic
(Aug 18, 2011)

germline

curation, clinical testing

PubMed (18)
[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	germline	unknown	6	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	10	not provided	not provided	10	not provided	curation

Citations

PubMed

Genetic microheterogeneity of human transthyretin detected by IEF.

Altland K, Benson MD, Costello CE, Ferlini A, Hazenberg BP, Hund E, Kristen AV, Linke RP, Merlini G, Salvi F, Saraiva MJ, Singer R, Skinner M, Winter P.

Electrophoresis. 2007 Jun;28(12):2053-64.

PubMed [citation]

PMID:: 17503405

Cardiac amyloidosis: report of a patient heterozygous for the transthyretin isoleucine 122 variant.

Saraiva MJ, Sherman W, Marboe C, Figueira A, Costa P, de Freitas AF, Gawinowicz MA.

Scand J Immunol. 1990 Oct;32(4):341-6.

PubMed [citation]

PMID:: 2237288

See all PubMed Citations (18)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000053250.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	10	not provided	not provided	curation	PubMed (18)
2	not provided	not provided	not provided	not provided	clinical testing	PubMed (18)
3	not provided	not provided	not provided	not provided	clinical testing	PubMed (18)
4	not provided	not provided	not provided	not provided	clinical testing	PubMed (18)
5	not provided	not provided	not provided	not provided	clinical testing	PubMed (18)
6	not provided	not provided	not provided	not provided	clinical testing	PubMed (18)
7	not provided	not provided	not provided	not provided	clinical testing	PubMed (18)

Description

"Common DV in African Americans causing Cardiac Amyloidosis; numbers entered here are fabricated to push the tbGP score to -3 since this is a known common DV; the review cited here states the following: "One particular mutation, Val122Ile, which is present in approximately 3% of African- Americans, causes restrictive cardiomyopathy in individuals usually after the age of 60. In this disease, in which neuropathy tends to be a minor factor and carpal tunnel syndrome the only neuropathic evidence of the disease, the diagnosis can be veryproblematic and any attempt to define penetrance is difficult."": PubMed [ID: 15123043]

Description

Converted during submission to Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	10	not provided	not provided		10	not provided	not provided	not provided
2	germline	unknown	not provided	Blood	assert pathogenicity		not provided	not provided	not provided	See 2
3	germline	unknown	not provided	Blood	assert pathogenicity		not provided	not provided	not provided	not provided
4	germline	unknown	not provided	Blood	assert pathogenicity		not provided	not provided	not provided	not provided
5	germline	unknown	not provided	Blood	assert pathogenicity		not provided	not provided	not provided	See 5
6	germline	unknown	not provided	Blood	assert pathogenicity		not provided	not provided	not provided	See 6
7	germline	unknown	not provided	Blood	assert pathogenicity		not provided	not provided	not provided	not provided

Co-occurrences

#	Zygosity	Alleles	Number of Observations
2	Homozygote	TTR:c.336+19G>A	1
5	SingleHeterozygote	TTR:c.336+19G>A	1
6	SingleHeterozygote	TTR:c.336+19G>A	1

Last Updated: Sep 16, 2024

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