TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14805	44638;44639;44640	chr2:178629312;178629311;178629310	chr2:179494039;179494038;179494037
N2AB	13164	39715;39716;39717	chr2:178629312;178629311;178629310	chr2:179494039;179494038;179494037
N2A	12237	36934;36935;36936	chr2:178629312;178629311;178629310	chr2:179494039;179494038;179494037
N2B	5740	17443;17444;17445	chr2:178629312;178629311;178629310	chr2:179494039;179494038;179494037
Novex-1	5865	17818;17819;17820	chr2:178629312;178629311;178629310	chr2:179494039;179494038;179494037
Novex-2	5932	18019;18020;18021	chr2:178629312;178629311;178629310	chr2:179494039;179494038;179494037
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-99
• Domain position: 41
• Structural Position: 70
• Q(SASA): 0.5316
• 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
P/S	None	None	1.0	N	0.717	0.325	0.362758974969	gnomAD-4.0.0	6.8475E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99965E-07	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
P/A	0.0692	likely_benign	0.0754	benign	-0.478	Destabilizing	1.0	D	0.664	neutral	N	0.500975008	None	None	N
P/C	0.5493	ambiguous	0.5846	pathogenic	-0.683	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
P/D	0.3144	likely_benign	0.3838	ambiguous	-0.452	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
P/E	0.2377	likely_benign	0.2868	benign	-0.565	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
P/F	0.4141	ambiguous	0.4712	ambiguous	-0.725	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	N
P/G	0.2541	likely_benign	0.2927	benign	-0.599	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
P/H	0.1787	likely_benign	0.2102	benign	-0.193	Destabilizing	1.0	D	0.629	neutral	D	0.578021121	None	None	N
P/I	0.2551	likely_benign	0.2929	benign	-0.308	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
P/K	0.2424	likely_benign	0.2945	benign	-0.536	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
P/L	0.108	likely_benign	0.1228	benign	-0.308	Destabilizing	1.0	D	0.744	deleterious	D	0.536256031	None	None	N
P/M	0.2755	likely_benign	0.3023	benign	-0.431	Destabilizing	1.0	D	0.631	neutral	None	None	None	None	N
P/N	0.2387	likely_benign	0.2871	benign	-0.297	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
P/Q	0.1461	likely_benign	0.1739	benign	-0.534	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
P/R	0.1619	likely_benign	0.1937	benign	-0.015	Destabilizing	1.0	D	0.697	prob.neutral	N	0.500752876	None	None	N
P/S	0.1114	likely_benign	0.1306	benign	-0.611	Destabilizing	1.0	D	0.717	prob.delet.	N	0.49871076	None	None	N
P/T	0.0916	likely_benign	0.1135	benign	-0.626	Destabilizing	1.0	D	0.705	prob.neutral	N	0.507709958	None	None	N
P/V	0.1737	likely_benign	0.1921	benign	-0.331	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
P/W	0.6027	likely_pathogenic	0.6737	pathogenic	-0.814	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	N
P/Y	0.3697	ambiguous	0.421	ambiguous	-0.522	Destabilizing	1.0	D	0.675	neutral	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.