Submissions for variant NM_000371.4(TTR):c.416C>T (p.Thr139Met) (rs28933981)

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine	RCV000036376	SCV000060029	likely benign	not specified	2012-05-02	criteria provided, single submitter	clinical testing	p.Thr139Met in exon 4 of TTR: This variant has been identified in 0.2% (164/6672 6) of European chromosomes from a broad population by the Exome Aggregation Cons ortium (ExAC, http://exac.broadinstitute.org/; dbSNP rs28933981). This variant h as been reported in both unaffected individuals as well as in individuals with a symptomatic euthyroid hyperthyroxinemia (Scrimshaw 1992, Alves 1997), and functi onal and clinical studies indicate that this variant may provide protective bene fit against TTR amyloidosis by improving protein stability and reducing the prop ensity to form amyloidogenic aggregates (Quintas 1997, Almeida 2000, Hammarstrom 2001, Costa 2008, Palhano 2009, Borgault 2011).
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	Amyloidogenic transthyretin amyloidosis	2019-12-31	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories	RCV001281790	SCV000605506	benign	none provided	2020-04-13	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000618448	SCV000735097	likely benign	Cardiovascular phenotype	2018-05-08	criteria provided, single submitter	clinical testing	In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Intact protein function observed in appropriate functional assay(s);Other strong data supporting benign classification;Subpopulation frequency in support of benign classification
Athena Diagnostics Inc	RCV000036376	SCV000844811	benign	not specified	2020-04-16	criteria provided, single submitter	clinical testing
Mendelics	RCV000990084	SCV001140875	likely benign	Amyloidogenic transthyretin amyloidosis	2019-05-28	criteria provided, single submitter	clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000714134	SCV001151528	uncertain significance	not provided	2018-08-01	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000990084	SCV001284998	benign	Amyloidogenic transthyretin amyloidosis	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
OMIM	RCV000014376	SCV000034625	risk factor	AMYLOIDOSIS, HEREDITARY, TRANSTHYRETIN-RELATED, MODIFIER OF	2001-09-28	no assertion criteria provided	literature only