Submissions for variant NM_000371.4(TTR):c.354C>T (p.Asn118=)

gnomAD frequency: 0.00009  dbSNP: rs11541797

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000152542	SCV000201746	likely benign	not specified	2012-03-19	criteria provided, single submitter	clinical testing	Asn118Asn in exon 4 of TTR: This variant is not expected to have clinical signif icance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 1/3738 African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS).
Ambry Genetics	RCV000242314	SCV000320423	likely benign	Cardiovascular phenotype	2015-11-11	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
GeneDx	RCV000152542	SCV000515196	likely benign	not specified	2017-08-02	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	RCV001081876	SCV000554846	likely benign	Familial amyloid neuropathy	2024-01-10	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000152542	SCV000616216	benign	not specified	2017-06-16	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000770557	SCV000902005	likely benign	Cardiomyopathy	2020-01-24	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000460535	SCV001151526	uncertain significance	not provided	2016-06-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001081876	SCV001283899	likely benign	Familial amyloid neuropathy	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000460535	SCV004565220	likely benign	not provided	2023-07-24	criteria provided, single submitter	clinical testing