TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14856	44791;44792;44793	chr2:178624714;178624713;178624712	chr2:179489441;179489440;179489439
N2AB	13215	39868;39869;39870	chr2:178624714;178624713;178624712	chr2:179489441;179489440;179489439
N2A	12288	37087;37088;37089	chr2:178624714;178624713;178624712	chr2:179489441;179489440;179489439
N2B	5791	17596;17597;17598	chr2:178624714;178624713;178624712	chr2:179489441;179489440;179489439
Novex-1	5916	17971;17972;17973	chr2:178624714;178624713;178624712	chr2:179489441;179489440;179489439
Novex-2	5983	18172;18173;18174	chr2:178624714;178624713;178624712	chr2:179489441;179489440;179489439
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-100
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.569
• 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/S	None	None	0.905	N	0.294	0.185	0.345859378078	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	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
T/A	0.1668	likely_benign	0.2097	benign	-0.787	Destabilizing	0.981	D	0.466	neutral	D	0.538309346	None	None	N
T/C	0.6742	likely_pathogenic	0.7459	pathogenic	-0.507	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
T/D	0.6891	likely_pathogenic	0.7485	pathogenic	-0.08	Destabilizing	0.999	D	0.728	prob.delet.	None	None	None	None	N
T/E	0.5106	ambiguous	0.5613	ambiguous	-0.074	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
T/F	0.4975	ambiguous	0.5866	pathogenic	-0.792	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
T/G	0.4524	ambiguous	0.5225	ambiguous	-1.053	Destabilizing	0.997	D	0.625	neutral	None	None	None	None	N
T/H	0.4644	ambiguous	0.5571	ambiguous	-1.252	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
T/I	0.2907	likely_benign	0.3581	ambiguous	-0.169	Destabilizing	0.999	D	0.745	deleterious	N	0.513545963	None	None	N
T/K	0.3607	ambiguous	0.4158	ambiguous	-0.697	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
T/L	0.1476	likely_benign	0.1931	benign	-0.169	Destabilizing	0.998	D	0.636	neutral	None	None	None	None	N
T/M	0.1738	likely_benign	0.2081	benign	0.048	Stabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
T/N	0.2824	likely_benign	0.3439	ambiguous	-0.635	Destabilizing	0.999	D	0.687	prob.neutral	D	0.598063258	None	None	N
T/P	0.4889	ambiguous	0.5204	ambiguous	-0.342	Destabilizing	1.0	D	0.742	deleterious	D	0.63187176	None	None	N
T/Q	0.3555	ambiguous	0.4219	ambiguous	-0.781	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
T/R	0.2799	likely_benign	0.3348	benign	-0.456	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
T/S	0.1612	likely_benign	0.2007	benign	-0.95	Destabilizing	0.905	D	0.294	neutral	N	0.507396605	None	None	N
T/V	0.2439	likely_benign	0.2827	benign	-0.342	Destabilizing	0.998	D	0.551	neutral	None	None	None	None	N
T/W	0.8117	likely_pathogenic	0.8601	pathogenic	-0.715	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
T/Y	0.5855	likely_pathogenic	0.6644	pathogenic	-0.492	Destabilizing	1.0	D	0.755	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.