Submissions for variant NM_000371.4(TTR):c.337-14_337-11del

dbSNP: rs112263266

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000155419	SCV000205109	benign	not specified	2018-08-10	criteria provided, single submitter	clinical testing	The c.337-14_337-11del variant in TTR is classified as benign because it has bee n identified in 0.3% (86/24008) of African chromsomes by gnomAD (http://gnomad.b roadinstitute.org) and is an intronic deletion of 1 of 2 GTCT tandem repeats tha t is not predicted to impact splicing. ACMG/AMP Criteria applied: BA1, BP4.
GeneDx	RCV000159406	SCV000209352	benign	Cardiomyopathy	2013-06-24	criteria provided, single submitter	clinical testing	The variant is found in HCM panel(s).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586853	SCV000696628	benign	not provided	2017-04-03	criteria provided, single submitter	clinical testing	Variant summary: The TTR c.337-14_337-11delGTCT variant involves the deletion of multiple intronic nucleotides. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 43/120050 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.003529 (36/10200). This frequency is about 113 times the estimated maximal expected allele frequency of a pathogenic TTR variant (0.0000313), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. One internally tested patient carries this variant and a pathogenic TTR variant (c.424G>A/p.Val142Ile), further supporting this variant is not associated with the disease. In addition, one clinical diagnostic laboratory classified this variant as benign. Taken together, this variant is classified as benign.
Athena Diagnostics	RCV000155419	SCV001476394	benign	not specified	2019-10-30	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000586853	SCV002049489	benign	not provided	2022-04-22	criteria provided, single submitter	clinical testing
Invitae	RCV001374654	SCV002463676	benign	Familial amyloid neuropathy	2024-01-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002453514	SCV002615536	uncertain significance	Cardiovascular phenotype	2019-08-26	criteria provided, single submitter	clinical testing	The c.337-14_337-11delGTCT intronic variant, located in intron 3 of the TTR gene, results from a deletion of 4 nucleotides within intron 3 of the TTR gene. This nucleotide position is not well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice acceptor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals	RCV001374654	SCV001571579	likely benign	Familial amyloid neuropathy	2021-01-06	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000155419	SCV001924218	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000586853	SCV001928416	likely benign	not provided		no assertion criteria provided	clinical testing