Submissions for variant NM_000371.4(TTR):c.384C>T (p.Ala128=)

gnomAD frequency: 0.00015  dbSNP: rs143906738

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000724798	SCV000230074	uncertain significance	not provided	2015-05-15	criteria provided, single submitter	clinical testing
GeneDx	RCV000178080	SCV000515198	benign	not specified	2016-02-18	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	RCV001086449	SCV000769151	likely benign	Familial amyloid neuropathy	2024-01-29	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000178080	SCV000967328	likely benign	not specified	2018-10-10	criteria provided, single submitter	clinical testing	The p.Ala128Ala variant in TTR is classified as likely benign because it does no t alter an amino acid residue, it is not located within the splice consensus seq uence, and splice prediction algorithms do not predict a newly created splice si te. It has also been identified in 0.01% (24/126672) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BP4, BP7, BS1_Supporting.
Athena Diagnostics	RCV000724798	SCV001146565	benign	not provided	2019-06-13	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001086449	SCV001284997	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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001170384	SCV001332961	likely benign	Cardiomyopathy	2020-03-20	criteria provided, single submitter	clinical testing
Molecular Genetics Laboratory, London Health Sciences Centre	RCV001173307	SCV001336391	likely benign	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002354458	SCV002621496	likely benign	Cardiovascular phenotype	2014-12-08	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.
PreventionGenetics, part of Exact Sciences	RCV004553003	SCV004767614	likely benign	TTR-related disorder	2019-11-21	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000178080	SCV005040464	benign	not specified	2024-03-03	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000178080	SCV001923176	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000724798	SCV001931738	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000724798	SCV001970099	likely benign	not provided		no assertion criteria provided	clinical testing