TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23536	70831;70832;70833	chr2:178575526;178575525;178575524	chr2:179440253;179440252;179440251
N2AB	21895	65908;65909;65910	chr2:178575526;178575525;178575524	chr2:179440253;179440252;179440251
N2A	20968	63127;63128;63129	chr2:178575526;178575525;178575524	chr2:179440253;179440252;179440251
N2B	14471	43636;43637;43638	chr2:178575526;178575525;178575524	chr2:179440253;179440252;179440251
Novex-1	14596	44011;44012;44013	chr2:178575526;178575525;178575524	chr2:179440253;179440252;179440251
Novex-2	14663	44212;44213;44214	chr2:178575526;178575525;178575524	chr2:179440253;179440252;179440251
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-59
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.1014
• 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/A	None	None	1.0	D	0.847	0.735	0.572793788404	gnomAD-4.0.0	1.59146E-06	None	None	None	None	N	None	0	0	None	0	2.77239E-05	None	0	0	0	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	0.8048	likely_pathogenic	0.7903	pathogenic	-2.428	Highly Destabilizing	1.0	D	0.847	deleterious	D	0.541675659	None	None	N
P/C	0.9724	likely_pathogenic	0.9764	pathogenic	-2.366	Highly Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
P/D	0.9988	likely_pathogenic	0.9989	pathogenic	-3.486	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
P/E	0.9955	likely_pathogenic	0.9957	pathogenic	-3.271	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
P/F	0.9979	likely_pathogenic	0.9978	pathogenic	-1.274	Destabilizing	1.0	D	0.945	deleterious	None	None	None	None	N
P/G	0.9927	likely_pathogenic	0.9929	pathogenic	-2.926	Highly Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
P/H	0.9959	likely_pathogenic	0.9959	pathogenic	-2.456	Highly Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	N
P/I	0.8348	likely_pathogenic	0.8509	pathogenic	-1.016	Destabilizing	1.0	D	0.951	deleterious	None	None	None	None	N
P/K	0.9976	likely_pathogenic	0.9977	pathogenic	-1.987	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
P/L	0.8491	likely_pathogenic	0.8531	pathogenic	-1.016	Destabilizing	1.0	D	0.93	deleterious	D	0.563792386	None	None	N
P/M	0.9645	likely_pathogenic	0.966	pathogenic	-1.401	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
P/N	0.998	likely_pathogenic	0.9982	pathogenic	-2.428	Highly Destabilizing	1.0	D	0.953	deleterious	None	None	None	None	N
P/Q	0.9921	likely_pathogenic	0.9916	pathogenic	-2.285	Highly Destabilizing	1.0	D	0.911	deleterious	D	0.554210507	None	None	N
P/R	0.9932	likely_pathogenic	0.9932	pathogenic	-1.76	Destabilizing	1.0	D	0.954	deleterious	D	0.576416139	None	None	N
P/S	0.9778	likely_pathogenic	0.9779	pathogenic	-2.959	Highly Destabilizing	1.0	D	0.892	deleterious	D	0.565313323	None	None	N
P/T	0.9095	likely_pathogenic	0.9131	pathogenic	-2.614	Highly Destabilizing	1.0	D	0.887	deleterious	D	0.57590916	None	None	N
P/V	0.6864	likely_pathogenic	0.717	pathogenic	-1.465	Destabilizing	1.0	D	0.931	deleterious	None	None	None	None	N
P/W	0.9995	likely_pathogenic	0.9996	pathogenic	-1.751	Destabilizing	1.0	D	0.92	deleterious	None	None	None	None	N
P/Y	0.9991	likely_pathogenic	0.9991	pathogenic	-1.504	Destabilizing	1.0	D	0.95	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.