TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5086	15481;15482;15483	chr2:178734568;178734567;178734566	chr2:179599295;179599294;179599293
N2AB	4769	14530;14531;14532	chr2:178734568;178734567;178734566	chr2:179599295;179599294;179599293
N2A	3842	11749;11750;11751	chr2:178734568;178734567;178734566	chr2:179599295;179599294;179599293
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-34
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.1978
• Predicted PPI site: I

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
I/T	rs938020572	None	None	N	0.225	0.302	0.58162856405	gnomAD-4.0.0	3.2832E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.8948E-06	0	0
I/V	rs1560838962	None	None	N	0.133	0.092	0.384086055536	gnomAD-2.1.1	4.27E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.78E-05	None	0	0	0
I/V	rs1560838962	None	None	N	0.133	0.092	0.384086055536	gnomAD-4.0.0	2.08059E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.08176E-07	2.42407E-05	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
I/A	0.3916	ambiguous	0.2562	benign	-1.535	Destabilizing	None	N	0.207	neutral	None	None	None	None	I
I/C	0.8522	likely_pathogenic	0.7483	pathogenic	-0.776	Destabilizing	0.356	N	0.423	neutral	None	None	None	None	I
I/D	0.9384	likely_pathogenic	0.8532	pathogenic	-0.705	Destabilizing	0.136	N	0.562	neutral	None	None	None	None	I
I/E	0.8549	likely_pathogenic	0.7293	pathogenic	-0.701	Destabilizing	0.136	N	0.504	neutral	None	None	None	None	I
I/F	0.3049	likely_benign	0.2198	benign	-1.164	Destabilizing	0.072	N	0.434	neutral	None	None	None	None	I
I/G	0.8691	likely_pathogenic	0.7164	pathogenic	-1.857	Destabilizing	0.031	N	0.393	neutral	None	None	None	None	I
I/H	0.8268	likely_pathogenic	0.6876	pathogenic	-1.178	Destabilizing	0.628	D	0.487	neutral	None	None	None	None	I
I/K	0.719	likely_pathogenic	0.5775	pathogenic	-0.851	Destabilizing	0.106	N	0.499	neutral	N	0.518595915	None	None	I
I/L	0.1956	likely_benign	0.1634	benign	-0.725	Destabilizing	None	N	0.127	neutral	N	0.474603117	None	None	I
I/M	0.1306	likely_benign	0.1094	benign	-0.513	Destabilizing	0.171	N	0.431	neutral	N	0.5152954	None	None	I
I/N	0.6775	likely_pathogenic	0.483	ambiguous	-0.619	Destabilizing	0.356	N	0.58	neutral	None	None	None	None	I
I/P	0.9562	likely_pathogenic	0.9053	pathogenic	-0.963	Destabilizing	0.136	N	0.561	neutral	None	None	None	None	I
I/Q	0.7917	likely_pathogenic	0.6323	pathogenic	-0.764	Destabilizing	0.628	D	0.561	neutral	None	None	None	None	I
I/R	0.6114	likely_pathogenic	0.455	ambiguous	-0.366	Destabilizing	0.295	N	0.583	neutral	N	0.518421197	None	None	I
I/S	0.5402	ambiguous	0.3628	ambiguous	-1.25	Destabilizing	0.016	N	0.355	neutral	None	None	None	None	I
I/T	0.19	likely_benign	0.1377	benign	-1.12	Destabilizing	None	N	0.225	neutral	N	0.45519289	None	None	I
I/V	0.0767	likely_benign	0.0662	benign	-0.963	Destabilizing	None	N	0.133	neutral	N	0.353748106	None	None	I
I/W	0.9237	likely_pathogenic	0.8736	pathogenic	-1.251	Destabilizing	0.864	D	0.491	neutral	None	None	None	None	I
I/Y	0.8124	likely_pathogenic	0.6977	pathogenic	-0.999	Destabilizing	0.356	N	0.503	neutral	None	None	None	None	I

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.