TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23638	71137;71138;71139	chr2:178575220;178575219;178575218	chr2:179439947;179439946;179439945
N2AB	21997	66214;66215;66216	chr2:178575220;178575219;178575218	chr2:179439947;179439946;179439945
N2A	21070	63433;63434;63435	chr2:178575220;178575219;178575218	chr2:179439947;179439946;179439945
N2B	14573	43942;43943;43944	chr2:178575220;178575219;178575218	chr2:179439947;179439946;179439945
Novex-1	14698	44317;44318;44319	chr2:178575220;178575219;178575218	chr2:179439947;179439946;179439945
Novex-2	14765	44518;44519;44520	chr2:178575220;178575219;178575218	chr2:179439947;179439946;179439945
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-130
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.9688
• 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	rs1709621384	None	0.989	N	0.479	0.4	0.686637490652	gnomAD-4.0.0	1.59336E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86053E-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
I/A	0.7496	likely_pathogenic	0.7816	pathogenic	-0.913	Destabilizing	0.992	D	0.536	neutral	None	None	None	None	I
I/C	0.7977	likely_pathogenic	0.8079	pathogenic	-0.906	Destabilizing	1.0	D	0.507	neutral	None	None	None	None	I
I/D	0.9438	likely_pathogenic	0.9492	pathogenic	-0.592	Destabilizing	1.0	D	0.589	neutral	None	None	None	None	I
I/E	0.9212	likely_pathogenic	0.9319	pathogenic	-0.616	Destabilizing	1.0	D	0.597	neutral	None	None	None	None	I
I/F	0.2265	likely_benign	0.2306	benign	-0.664	Destabilizing	0.998	D	0.48	neutral	N	0.475931251	None	None	I
I/G	0.9169	likely_pathogenic	0.9264	pathogenic	-1.138	Destabilizing	1.0	D	0.597	neutral	None	None	None	None	I
I/H	0.7888	likely_pathogenic	0.8123	pathogenic	-0.305	Destabilizing	1.0	D	0.598	neutral	None	None	None	None	I
I/K	0.8159	likely_pathogenic	0.8351	pathogenic	-0.719	Destabilizing	1.0	D	0.595	neutral	None	None	None	None	I
I/L	0.144	likely_benign	0.1487	benign	-0.4	Destabilizing	0.889	D	0.409	neutral	N	0.443701402	None	None	I
I/M	0.1672	likely_benign	0.1764	benign	-0.665	Destabilizing	0.998	D	0.497	neutral	N	0.476104609	None	None	I
I/N	0.5868	likely_pathogenic	0.6173	pathogenic	-0.657	Destabilizing	0.999	D	0.593	neutral	N	0.476798043	None	None	I
I/P	0.9427	likely_pathogenic	0.9468	pathogenic	-0.541	Destabilizing	1.0	D	0.593	neutral	None	None	None	None	I
I/Q	0.8192	likely_pathogenic	0.8408	pathogenic	-0.781	Destabilizing	1.0	D	0.589	neutral	None	None	None	None	I
I/R	0.7481	likely_pathogenic	0.767	pathogenic	-0.215	Destabilizing	1.0	D	0.594	neutral	None	None	None	None	I
I/S	0.6797	likely_pathogenic	0.7126	pathogenic	-1.109	Destabilizing	0.998	D	0.498	neutral	N	0.475757893	None	None	I
I/T	0.675	likely_pathogenic	0.7198	pathogenic	-1.015	Destabilizing	0.989	D	0.479	neutral	N	0.475237818	None	None	I
I/V	0.1154	likely_benign	0.1221	benign	-0.541	Destabilizing	0.333	N	0.306	neutral	N	0.425982433	None	None	I
I/W	0.873	likely_pathogenic	0.8685	pathogenic	-0.713	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	I
I/Y	0.6206	likely_pathogenic	0.6218	pathogenic	-0.484	Destabilizing	1.0	D	0.471	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.