Submissions for variant NM_001267550.2(TTN):c.4153G>A (p.Ala1385Thr)

gnomAD frequency: 0.00005  dbSNP: rs140760859

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000172478	SCV000051344	uncertain significance	not provided	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000155013	SCV000204695	uncertain significance	not specified	2013-04-02	criteria provided, single submitter	clinical testing	The Ala1385Thr variant in TTN has been identified by our laboratory in 1 infant with DCM (LMM unpublished data). This variant has been identified in 1/4406 Afri can American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.wa shington.edu/EVS/) and in 1/1324 European chromosomes by the ClinSeq Project (db SNP rs140760859). Computational analyses (biochemical amino acid properties, con servation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Additional information is needed to fully asse ss the clinical significance of this variant.
Invitae	RCV000464939	SCV000542704	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-06-06	criteria provided, single submitter	clinical testing
GeneDx	RCV000172478	SCV000725614	likely benign	not provided	2019-06-18	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 23861362)
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769134	SCV000900508	uncertain significance	Cardiomyopathy	2020-08-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002354371	SCV002622213	uncertain significance	Cardiovascular phenotype	2020-08-18	criteria provided, single submitter	clinical testing	The p.A1339T variant (also known as c.4015G>A), located in coding exon 22 of the TTN gene, results from a G to A substitution at nucleotide position 4015. The alanine at codon 1339 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV000172478	SCV003820298	uncertain significance	not provided	2019-12-26	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000172478	SCV004183842	uncertain significance	not provided	2023-11-01	criteria provided, single submitter	clinical testing	TTN: PM2