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NM_000371.3(TTR):c.379A>G (p.Ile127Val)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
8 (Most recent: Jul 4, 2021)
Last evaluated:
Oct 23, 2020
Accession:
VCV000013450.12
Variation ID:
13450
Description:
single nucleotide variant
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NM_000371.3(TTR):c.379A>G (p.Ile127Val)

Allele ID
28489
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
18q12.1
Genomic location
18: 31598610 (GRCh38) GRCh38 UCSC
18: 29178573 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000018.10:g.31598610A>G
NC_000018.9:g.29178573A>G
NM_000371.3:c.379A>G NP_000362.1:p.Ile127Val missense
... more HGVS
Protein change
I127V
Other names
I107V
Canonical SPDI
NC_000018.10:31598609:A:G
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA256843
UniProtKB: P02766#VAR_007592
OMIM: 176300.0034
dbSNP: rs121918089
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 4 criteria provided, multiple submitters, no conflicts Aug 27, 2020 RCV000014392.21
Pathogenic 3 criteria provided, multiple submitters, no conflicts Oct 23, 2020 RCV001090344.3
Likely pathogenic 1 criteria provided, single submitter Mar 1, 2017 RCV000506089.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
TTR - - GRCh38
GRCh37
235 275

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Feb 26, 2016)
criteria provided, single submitter
Method: clinical testing
Amyloidogenic transthyretin amyloidosis
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000696632.1
Submitted: (Jan 25, 2018)
Evidence details
Publications
PubMed (8)
Comment:
Variant summary: The TTR c.379A>G variant affects a conserved nucleotide, resulting in amino acid change from Ile to Val. 3/4 in-silico tools predict this variant … (more)
Pathogenic
(May 28, 2019)
criteria provided, single submitter
Method: clinical testing
Amyloidogenic transthyretin amyloidosis
Allele origin: unknown
Mendelics
Accession: SCV001140874.1
Submitted: (Oct 22, 2019)
Evidence details
Pathogenic
(Aug 27, 2020)
criteria provided, single submitter
Method: clinical testing
Amyloidogenic transthyretin amyloidosis
Allele origin: germline
Invitae
Accession: SCV000769146.4
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (11)
Comment:
This sequence change replaces isoleucine with valine at codon 127 of the TTR protein (p.Ile127Val). The isoleucine residue is highly conserved and there is a … (more)
Pathogenic
(Mar 01, 2019)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
CeGaT Praxis fuer Humangenetik Tuebingen
Accession: SCV001245843.5
Submitted: (Jul 04, 2021)
Evidence details
Likely pathogenic
(Mar 01, 2017)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories
Accession: SCV000605507.1
Submitted: (Jun 30, 2017)
Evidence details
Pathogenic
(Oct 23, 2020)
criteria provided, single submitter
Method: clinical testing
not provided
(Autosomal dominant inheritance)
Allele origin: germline
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001446722.1
Submitted: (Oct 23, 2020)
Evidence details
Pathogenic
(Dec 16, 2019)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: unknown
Athena Diagnostics Inc
Accession: SCV001476395.1
Submitted: (Dec 30, 2020)
Evidence details
Publications
PubMed (10)
Comment:
Not found in the total gnomAD dataset, and the data is high quality. Found in multiple individuals with expected phenotype for this gene. Assessment of … (more)
Pathogenic
(May 01, 1994)
no assertion criteria provided
Method: literature only
AMYLOIDOSIS, HEREDITARY, TRANSTHYRETIN-RELATED
Allele origin: germline
OMIM
Accession: SCV000034641.1
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (1)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
A case of familial amyloid polyneuropathy (FAP ATTR Ile107Val) with proximal muscle weakness in the lower extremities. Kuzume D Rinsho shinkeigaku = Clinical neurology 2016 PMID: 27025994
Prevalence and clinical phenotype of hereditary transthyretin amyloid cardiomyopathy in patients with increased left ventricular wall thickness. Damy T European heart journal 2016 PMID: 26537620
Tongue atrophy and fasciculations in transthyretin familial amyloid neuropathy: An ALS mimicker. Goyal NA Neurology. Genetics 2015 PMID: 27066555
Multimodal retinal imaging in a Chinese kindred with familial amyloid polyneuropathy secondary to transthyretin Ile107Met mutation. Lv W Eye (London, England) 2014 PMID: 24480837
Diagnostic hallmarks and pitfalls in late-onset progressive transthyretin-related amyloid-neuropathy. Dohrn MF Journal of neurology 2013 PMID: 24101130
Disease profile and differential diagnosis of hereditary transthyretin-related amyloidosis with exclusively cardiac phenotype: an Italian perspective. Rapezzi C European heart journal 2013 PMID: 22745357
Liver transplantation and combined liver-heart transplantation in patients with familial amyloid polyneuropathy: a single-center experience. Barreiros AP Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 2010 PMID: 20209591
Cardiac amyloidosis in African Americans: comparison of clinical and laboratory features of transthyretin V122I amyloidosis and immunoglobulin light chain amyloidosis. Connors LH American heart journal 2009 PMID: 19781421
Genetic microheterogeneity of human transthyretin detected by IEF. Altland K Electrophoresis 2007 PMID: 17503405
The hereditary amyloidoses. Benson MD Best practice & research. Clinical rheumatology 2003 PMID: 15123043
Transthyretin Val 107 in a Japanese patient with familial amyloid polyneuropathy. Nanri K Journal of the neurological sciences 2002 PMID: 12039669
Genotypic-phenotypic variations in a series of 65 patients with familial amyloid polyneuropathy. Planté-Bordeneuve V Neurology 1998 PMID: 9748014
Transthyretin VAL107, a new variant associated with familial cardiac and neuropathic amyloidosis. Jacobson DR Human mutation 1994 PMID: 8081397
Amyloid polyneuropathy in two German-American families: a new transthyretin variant (Val 107). Uemichi T Journal of medical genetics 1994 PMID: 7914929

Text-mined citations for rs121918089...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jul 10, 2021