TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32559	97900;97901;97902	chr2:178541402;178541401;178541400	chr2:179406129;179406128;179406127
N2AB	30918	92977;92978;92979	chr2:178541402;178541401;178541400	chr2:179406129;179406128;179406127
N2A	29991	90196;90197;90198	chr2:178541402;178541401;178541400	chr2:179406129;179406128;179406127
N2B	23494	70705;70706;70707	chr2:178541402;178541401;178541400	chr2:179406129;179406128;179406127
Novex-1	23619	71080;71081;71082	chr2:178541402;178541401;178541400	chr2:179406129;179406128;179406127
Novex-2	23686	71281;71282;71283	chr2:178541402;178541401;178541400	chr2:179406129;179406128;179406127
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-125
• Domain position: 61
• Structural Position: 91
• Q(SASA): 0.2487
• 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
Y/C	None	None	1.0	N	0.776	0.488	0.574195325796	gnomAD-4.0.0	1.59428E-06	None	None	None	None	I	None	0	0	None	0	2.77994E-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
Y/A	0.932	likely_pathogenic	0.9408	pathogenic	-2.325	Highly Destabilizing	0.998	D	0.618	neutral	None	None	None	None	I
Y/C	0.3177	likely_benign	0.3605	ambiguous	-1.319	Destabilizing	1.0	D	0.776	deleterious	N	0.508787457	None	None	I
Y/D	0.9661	likely_pathogenic	0.9695	pathogenic	-1.697	Destabilizing	1.0	D	0.778	deleterious	D	0.525017349	None	None	I
Y/E	0.9772	likely_pathogenic	0.9784	pathogenic	-1.542	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
Y/F	0.0912	likely_benign	0.0866	benign	-0.751	Destabilizing	0.434	N	0.353	neutral	N	0.441773031	None	None	I
Y/G	0.9051	likely_pathogenic	0.9196	pathogenic	-2.696	Highly Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
Y/H	0.6581	likely_pathogenic	0.6638	pathogenic	-1.131	Destabilizing	1.0	D	0.719	prob.delet.	D	0.527373218	None	None	I
Y/I	0.7702	likely_pathogenic	0.7778	pathogenic	-1.156	Destabilizing	0.999	D	0.63	neutral	None	None	None	None	I
Y/K	0.9678	likely_pathogenic	0.9647	pathogenic	-1.695	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
Y/L	0.64	likely_pathogenic	0.6493	pathogenic	-1.156	Destabilizing	0.994	D	0.469	neutral	None	None	None	None	I
Y/M	0.8063	likely_pathogenic	0.8132	pathogenic	-0.924	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
Y/N	0.8481	likely_pathogenic	0.8701	pathogenic	-2.324	Highly Destabilizing	1.0	D	0.773	deleterious	D	0.524763859	None	None	I
Y/P	0.9971	likely_pathogenic	0.9974	pathogenic	-1.548	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
Y/Q	0.9343	likely_pathogenic	0.9381	pathogenic	-2.095	Highly Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	I
Y/R	0.9301	likely_pathogenic	0.93	pathogenic	-1.435	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
Y/S	0.8511	likely_pathogenic	0.8763	pathogenic	-2.774	Highly Destabilizing	1.0	D	0.702	prob.neutral	N	0.498012324	None	None	I
Y/T	0.9404	likely_pathogenic	0.9478	pathogenic	-2.51	Highly Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
Y/V	0.7285	likely_pathogenic	0.7319	pathogenic	-1.548	Destabilizing	0.997	D	0.594	neutral	None	None	None	None	I
Y/W	0.6148	likely_pathogenic	0.6298	pathogenic	-0.251	Destabilizing	1.0	D	0.706	prob.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.