Submissions for variant NM_000371.4(TTR):c.360C>T (p.Ser120=)

gnomAD frequency: 0.00128  dbSNP: rs150127220

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036374	SCV000060027	benign	not specified	2015-03-11	criteria provided, single submitter	clinical testing	p.Ser120Ser in exon 4 of TTR: This variant is not expected to have clinical sign ificance because it has been identified in 3.5% (300/8636) of East Asian chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs150127220).
Labcorp Genetics (formerly Invitae), Labcorp	RCV000206233	SCV000261520	benign	Amyloidosis, hereditary systemic 1	2025-02-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000253403	SCV000317523	benign	Cardiovascular phenotype	2014-12-18	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Illumina Laboratory Services, Illumina	RCV000206233	SCV000408395	benign	Amyloidosis, hereditary systemic 1	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Athena Diagnostics	RCV000036374	SCV000616217	benign	not specified	2017-02-15	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589654	SCV000696630	benign	not provided	2016-06-22	criteria provided, single submitter	clinical testing	Variant summary: The TTR c.360C>T (p.Ser120Ser) variant causes a synonymous change involving a non-conserved nucleotide with 5/5 splice prediction tools predicting no significant impact on splicing and ESE finder predicts changes of binding motifs for RNA splicing enhancers, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 339/121120 (1/357, 7 homozygotes), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic TTR variant of 1/31948 (0.0000313), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories classified this variant as benign. Taken together, this variant is classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000589654	SCV000884815	benign	not provided	2023-11-03	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000770560	SCV000902008	benign	Cardiomyopathy	2017-07-10	criteria provided, single submitter	clinical testing
Molecular Genetics Laboratory, London Health Sciences Centre	RCV001173544	SCV001336634	benign	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
GeneDx	RCV000589654	SCV001850236	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000036374	SCV002066692	benign	not specified	2021-11-19	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000589654	SCV001741043	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000036374	SCV001923451	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000036374	SCV001927228	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000036374	SCV001952427	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000589654	SCV001975573	likely benign	not provided		no assertion criteria provided	clinical testing
Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals	RCV000206233	SCV002029169	likely benign	Amyloidosis, hereditary systemic 1	2021-10-18	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000036374	SCV002035384	benign	not specified		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004549443	SCV004756062	benign	TTR-related disorder	2019-05-29	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).