TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20119	60580;60581;60582	chr2:178591370;178591369;178591368	chr2:179456097;179456096;179456095
N2AB	18478	55657;55658;55659	chr2:178591370;178591369;178591368	chr2:179456097;179456096;179456095
N2A	17551	52876;52877;52878	chr2:178591370;178591369;178591368	chr2:179456097;179456096;179456095
N2B	11054	33385;33386;33387	chr2:178591370;178591369;178591368	chr2:179456097;179456096;179456095
Novex-1	11179	33760;33761;33762	chr2:178591370;178591369;178591368	chr2:179456097;179456096;179456095
Novex-2	11246	33961;33962;33963	chr2:178591370;178591369;178591368	chr2:179456097;179456096;179456095
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-120
• Domain position: 40
• Structural Position: 58
• Q(SASA): 0.1338
• 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
I/T	None	None	0.998	D	0.669	0.555	0.754645211913	gnomAD-4.0.0	1.59219E-06	None	None	None	None	N	None	5.66508E-05	0	None	0	0	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
I/A	0.8479	likely_pathogenic	0.8591	pathogenic	-2.215	Highly Destabilizing	0.996	D	0.538	neutral	None	None	None	None	N
I/C	0.8838	likely_pathogenic	0.8916	pathogenic	-1.696	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
I/D	0.9803	likely_pathogenic	0.9817	pathogenic	-1.666	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
I/E	0.9389	likely_pathogenic	0.9427	pathogenic	-1.481	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
I/F	0.313	likely_benign	0.3484	ambiguous	-1.308	Destabilizing	0.997	D	0.606	neutral	D	0.528040513	None	None	N
I/G	0.9522	likely_pathogenic	0.9563	pathogenic	-2.73	Highly Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
I/H	0.9251	likely_pathogenic	0.9283	pathogenic	-2.037	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
I/K	0.8423	likely_pathogenic	0.8481	pathogenic	-1.549	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
I/L	0.1296	likely_benign	0.1369	benign	-0.765	Destabilizing	0.104	N	0.245	neutral	N	0.438431656	None	None	N
I/M	0.138	likely_benign	0.1437	benign	-0.822	Destabilizing	0.997	D	0.633	neutral	N	0.490851479	None	None	N
I/N	0.8413	likely_pathogenic	0.8513	pathogenic	-1.71	Destabilizing	0.999	D	0.826	deleterious	N	0.503475232	None	None	N
I/P	0.949	likely_pathogenic	0.9525	pathogenic	-1.224	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
I/Q	0.8812	likely_pathogenic	0.8847	pathogenic	-1.607	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
I/R	0.8094	likely_pathogenic	0.8167	pathogenic	-1.289	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
I/S	0.9063	likely_pathogenic	0.9131	pathogenic	-2.53	Highly Destabilizing	0.999	D	0.715	prob.delet.	N	0.516957905	None	None	N
I/T	0.8707	likely_pathogenic	0.8796	pathogenic	-2.185	Highly Destabilizing	0.998	D	0.669	neutral	D	0.532273775	None	None	N
I/V	0.1398	likely_benign	0.1404	benign	-1.224	Destabilizing	0.889	D	0.405	neutral	N	0.458100426	None	None	N
I/W	0.9005	likely_pathogenic	0.9073	pathogenic	-1.518	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
I/Y	0.7625	likely_pathogenic	0.7836	pathogenic	-1.243	Destabilizing	1.0	D	0.726	prob.delet.	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.