ClinVar Miner

Submissions for variant NM_000371.4(TTR):c.416C>T (p.Thr139Met)

gnomAD frequency: 0.00177  dbSNP: rs28933981
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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000036376 SCV000060029 benign not specified 2021-09-15 criteria provided, single submitter clinical testing The p.Thr139Met variant in TTR is classified as benign because it has been identified in 0.3% (351/129156) of European chromosomes by gnomAD ( Additionally, this variant has been reported in both unaffected individuals as well as in individuals with asymptomatic euthyroid hyperthyroxinemia (Scrimshaw 1992, Alves 1997). Functional and clinical studies indicate that this variant may provide protective benefit against TTR amyloidosis by improving protein stability and reducing the propensity to form amyloidogenic aggregates (Quintas 1997, Almeida 2000, Hammarstrom 2001, Costa 2008, Palhano 2009, Borgault 2011). ACMG/AMP Criteria applied: BA1.
GeneDx RCV000036376 SCV000169669 benign not specified 2013-05-22 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000990084 SCV000554851 benign Familial amyloid neuropathy 2024-01-29 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000714134 SCV000605506 benign not provided 2023-11-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV000618448 SCV000735097 likely benign Cardiovascular phenotype 2018-05-08 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Athena Diagnostics RCV000036376 SCV000844811 benign not specified 2020-12-22 criteria provided, single submitter clinical testing
Mendelics RCV000990084 SCV001140875 likely benign Familial amyloid neuropathy 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000714134 SCV001151528 likely benign not provided 2024-04-01 criteria provided, single submitter clinical testing TTR: BS1
Illumina Laboratory Services, Illumina RCV000990084 SCV001284998 benign Familial amyloid neuropathy 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001170385 SCV001332962 benign Cardiomyopathy 2018-06-21 criteria provided, single submitter clinical testing
Molecular Genetics Laboratory, London Health Sciences Centre RCV001173303 SCV001336387 likely benign Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Cambridge Genomics Laboratory, East Genomic Laboratory Hub, NHS Genomic Medicine Service RCV003993656 SCV004809208 likely pathogenic Hyperthyroxinemia, dystransthyretinemic 2023-09-01 criteria provided, single submitter clinical testing PS3,PS4_Moderate,PP4
OMIM RCV000014376 SCV000034625 risk factor AMYLOIDOSIS, HEREDITARY SYSTEMIC 1, MODIFIER OF 2001-09-28 no assertion criteria provided literature only
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000714134 SCV001969591 likely benign not provided no assertion criteria provided clinical testing

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