TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8154	24685;24686;24687	chr2:178718740;178718739;178718738	chr2:179583467;179583466;179583465
N2AB	7837	23734;23735;23736	chr2:178718740;178718739;178718738	chr2:179583467;179583466;179583465
N2A	6910	20953;20954;20955	chr2:178718740;178718739;178718738	chr2:179583467;179583466;179583465
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-66
• Domain position: 77
• Structural Position: 161
• Q(SASA): 0.1534
• 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
N/D	rs757293293	-1.492	0.999	D	0.605	0.623	0.361958692863	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
N/D	rs757293293	-1.492	0.999	D	0.605	0.623	0.361958692863	gnomAD-4.0.0	3.18254E-06	None	None	None	None	N	None	0	4.57247E-05	None	0	0	None	0	0	0	0	0
N/S	rs749455191	-1.209	0.999	N	0.571	0.621	0.258283824007	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
N/S	rs749455191	-1.209	0.999	N	0.571	0.621	0.258283824007	gnomAD-4.0.0	2.73685E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.6379E-05	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
N/A	0.95	likely_pathogenic	0.9567	pathogenic	-0.874	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
N/C	0.9141	likely_pathogenic	0.9296	pathogenic	-0.247	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
N/D	0.883	likely_pathogenic	0.901	pathogenic	-1.353	Destabilizing	0.999	D	0.605	neutral	D	0.537281799	None	None	N
N/E	0.9931	likely_pathogenic	0.9929	pathogenic	-1.23	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
N/F	0.9983	likely_pathogenic	0.9983	pathogenic	-0.662	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
N/G	0.8898	likely_pathogenic	0.8977	pathogenic	-1.215	Destabilizing	0.999	D	0.551	neutral	None	None	None	None	N
N/H	0.9169	likely_pathogenic	0.9205	pathogenic	-0.961	Destabilizing	1.0	D	0.738	prob.delet.	N	0.512051201	None	None	N
N/I	0.9825	likely_pathogenic	0.9839	pathogenic	-0.001	Destabilizing	1.0	D	0.718	prob.delet.	D	0.550159041	None	None	N
N/K	0.9923	likely_pathogenic	0.9928	pathogenic	-0.272	Destabilizing	1.0	D	0.733	prob.delet.	D	0.549398573	None	None	N
N/L	0.9616	likely_pathogenic	0.9658	pathogenic	-0.001	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
N/M	0.9788	likely_pathogenic	0.9808	pathogenic	0.466	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
N/P	0.9904	likely_pathogenic	0.9876	pathogenic	-0.263	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
N/Q	0.9914	likely_pathogenic	0.9917	pathogenic	-1.054	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
N/R	0.9883	likely_pathogenic	0.9879	pathogenic	-0.263	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
N/S	0.3215	likely_benign	0.3356	benign	-0.997	Destabilizing	0.999	D	0.571	neutral	N	0.49841349	None	None	N
N/T	0.7738	likely_pathogenic	0.7942	pathogenic	-0.693	Destabilizing	0.999	D	0.701	prob.neutral	N	0.519431033	None	None	N
N/V	0.9657	likely_pathogenic	0.9683	pathogenic	-0.263	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
N/W	0.9992	likely_pathogenic	0.999	pathogenic	-0.452	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
N/Y	0.9804	likely_pathogenic	0.9784	pathogenic	-0.177	Destabilizing	1.0	D	0.74	deleterious	D	0.549905552	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.