TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26349	79270;79271;79272	chr2:178567087;178567086;178567085	chr2:179431814;179431813;179431812
N2AB	24708	74347;74348;74349	chr2:178567087;178567086;178567085	chr2:179431814;179431813;179431812
N2A	23781	71566;71567;71568	chr2:178567087;178567086;178567085	chr2:179431814;179431813;179431812
N2B	17284	52075;52076;52077	chr2:178567087;178567086;178567085	chr2:179431814;179431813;179431812
Novex-1	17409	52450;52451;52452	chr2:178567087;178567086;178567085	chr2:179431814;179431813;179431812
Novex-2	17476	52651;52652;52653	chr2:178567087;178567086;178567085	chr2:179431814;179431813;179431812
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-79
• Domain position: 64
• Structural Position: 94
• Q(SASA): 0.3748
• Predicted PPI site: N

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
T/A	None	None	0.928	N	0.43	0.36	0.319970858106	gnomAD-4.0.0	3.601E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62502E-06	0	3.66354E-05

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
T/A	0.1719	likely_benign	0.1776	benign	-0.483	Destabilizing	0.928	D	0.43	neutral	N	0.517713585	None	None	N
T/C	0.5567	ambiguous	0.544	ambiguous	-0.355	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
T/D	0.782	likely_pathogenic	0.7817	pathogenic	0.279	Stabilizing	0.997	D	0.748	deleterious	None	None	None	None	N
T/E	0.7407	likely_pathogenic	0.7016	pathogenic	0.254	Stabilizing	0.997	D	0.745	deleterious	None	None	None	None	N
T/F	0.4993	ambiguous	0.4493	ambiguous	-0.665	Destabilizing	0.983	D	0.79	deleterious	None	None	None	None	N
T/G	0.2838	likely_benign	0.2874	benign	-0.694	Destabilizing	0.992	D	0.671	neutral	None	None	None	None	N
T/H	0.5282	ambiguous	0.5042	ambiguous	-0.861	Destabilizing	0.999	D	0.766	deleterious	None	None	None	None	N
T/I	0.4471	ambiguous	0.4105	ambiguous	-0.03	Destabilizing	0.085	N	0.261	neutral	N	0.492060841	None	None	N
T/K	0.6143	likely_pathogenic	0.5585	ambiguous	-0.494	Destabilizing	0.992	D	0.749	deleterious	None	None	None	None	N
T/L	0.1864	likely_benign	0.1686	benign	-0.03	Destabilizing	0.745	D	0.487	neutral	None	None	None	None	N
T/M	0.1409	likely_benign	0.1377	benign	-0.014	Destabilizing	0.996	D	0.771	deleterious	None	None	None	None	N
T/N	0.2216	likely_benign	0.2277	benign	-0.346	Destabilizing	0.996	D	0.651	neutral	N	0.520791175	None	None	N
T/P	0.1901	likely_benign	0.2325	benign	-0.149	Destabilizing	0.996	D	0.781	deleterious	N	0.47020715	None	None	N
T/Q	0.4493	ambiguous	0.4233	ambiguous	-0.48	Destabilizing	0.997	D	0.787	deleterious	None	None	None	None	N
T/R	0.588	likely_pathogenic	0.5286	ambiguous	-0.248	Destabilizing	0.997	D	0.782	deleterious	None	None	None	None	N
T/S	0.1548	likely_benign	0.1619	benign	-0.622	Destabilizing	0.963	D	0.407	neutral	N	0.484291657	None	None	N
T/V	0.2933	likely_benign	0.2665	benign	-0.149	Destabilizing	0.547	D	0.444	neutral	None	None	None	None	N
T/W	0.8106	likely_pathogenic	0.752	pathogenic	-0.656	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
T/Y	0.6037	likely_pathogenic	0.5332	ambiguous	-0.4	Destabilizing	0.992	D	0.793	deleterious	None	None	None	None	N

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.