TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23564	70915;70916;70917	chr2:178575442;178575441;178575440	chr2:179440169;179440168;179440167
N2AB	21923	65992;65993;65994	chr2:178575442;178575441;178575440	chr2:179440169;179440168;179440167
N2A	20996	63211;63212;63213	chr2:178575442;178575441;178575440	chr2:179440169;179440168;179440167
N2B	14499	43720;43721;43722	chr2:178575442;178575441;178575440	chr2:179440169;179440168;179440167
Novex-1	14624	44095;44096;44097	chr2:178575442;178575441;178575440	chr2:179440169;179440168;179440167
Novex-2	14691	44296;44297;44298	chr2:178575442;178575441;178575440	chr2:179440169;179440168;179440167
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: Fn3-59
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1603
• 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/F	None	None	1.0	D	0.833	0.543	0.654604268507	gnomAD-4.0.0	1.5917E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85927E-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	0.9742	likely_pathogenic	0.9743	pathogenic	-2.284	Highly Destabilizing	1.0	D	0.642	neutral	None	None	None	None	I
I/C	0.9775	likely_pathogenic	0.9796	pathogenic	-1.448	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	I
I/D	0.9958	likely_pathogenic	0.9958	pathogenic	-1.897	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
I/E	0.9901	likely_pathogenic	0.9903	pathogenic	-1.813	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	I
I/F	0.9279	likely_pathogenic	0.9348	pathogenic	-1.549	Destabilizing	1.0	D	0.833	deleterious	D	0.523055566	None	None	I
I/G	0.9936	likely_pathogenic	0.994	pathogenic	-2.712	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
I/H	0.9927	likely_pathogenic	0.9936	pathogenic	-1.922	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
I/K	0.9877	likely_pathogenic	0.9883	pathogenic	-1.578	Destabilizing	0.998	D	0.859	deleterious	None	None	None	None	I
I/L	0.4797	ambiguous	0.5186	ambiguous	-1.116	Destabilizing	0.955	D	0.414	neutral	N	0.482719225	None	None	I
I/M	0.5601	ambiguous	0.5696	pathogenic	-0.843	Destabilizing	0.999	D	0.809	deleterious	D	0.543694716	None	None	I
I/N	0.8442	likely_pathogenic	0.843	pathogenic	-1.505	Destabilizing	1.0	D	0.855	deleterious	D	0.537960724	None	None	I
I/P	0.9614	likely_pathogenic	0.9664	pathogenic	-1.479	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
I/Q	0.9891	likely_pathogenic	0.99	pathogenic	-1.603	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
I/R	0.9847	likely_pathogenic	0.9859	pathogenic	-1.022	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
I/S	0.9666	likely_pathogenic	0.9668	pathogenic	-2.222	Highly Destabilizing	1.0	D	0.848	deleterious	D	0.537200256	None	None	I
I/T	0.9438	likely_pathogenic	0.9445	pathogenic	-2.007	Highly Destabilizing	1.0	D	0.808	deleterious	N	0.52107101	None	None	I
I/V	0.1398	likely_benign	0.1498	benign	-1.479	Destabilizing	0.966	D	0.4	neutral	N	0.509056816	None	None	I
I/W	0.9975	likely_pathogenic	0.9977	pathogenic	-1.707	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
I/Y	0.9807	likely_pathogenic	0.9816	pathogenic	-1.492	Destabilizing	0.999	D	0.819	deleterious	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.