TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34155	102688;102689;102690	chr2:178534152;178534151;178534150	chr2:179398879;179398878;179398877
N2AB	32514	97765;97766;97767	chr2:178534152;178534151;178534150	chr2:179398879;179398878;179398877
N2A	31587	94984;94985;94986	chr2:178534152;178534151;178534150	chr2:179398879;179398878;179398877
N2B	25090	75493;75494;75495	chr2:178534152;178534151;178534150	chr2:179398879;179398878;179398877
Novex-1	25215	75868;75869;75870	chr2:178534152;178534151;178534150	chr2:179398879;179398878;179398877
Novex-2	25282	76069;76070;76071	chr2:178534152;178534151;178534150	chr2:179398879;179398878;179398877
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-160
• Domain position: 19
• Structural Position: 30
• Q(SASA): 0.1107
• 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
Y/H	None	None	0.975	N	0.604	0.569	0.405839309607	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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
Y/A	0.971	likely_pathogenic	0.9678	pathogenic	-2.455	Highly Destabilizing	0.665	D	0.689	prob.neutral	None	None	None	None	N
Y/C	0.8168	likely_pathogenic	0.8405	pathogenic	-1.334	Destabilizing	0.993	D	0.815	deleterious	N	0.43048975	None	None	N
Y/D	0.9905	likely_pathogenic	0.9915	pathogenic	-3.212	Highly Destabilizing	0.975	D	0.783	deleterious	N	0.430663108	None	None	N
Y/E	0.9958	likely_pathogenic	0.9959	pathogenic	-2.968	Highly Destabilizing	0.981	D	0.762	deleterious	None	None	None	None	N
Y/F	0.1171	likely_benign	0.1329	benign	-0.817	Destabilizing	0.001	N	0.206	neutral	N	0.267303066	None	None	N
Y/G	0.9575	likely_pathogenic	0.9522	pathogenic	-2.897	Highly Destabilizing	0.828	D	0.726	prob.delet.	None	None	None	None	N
Y/H	0.9559	likely_pathogenic	0.9588	pathogenic	-2.057	Highly Destabilizing	0.975	D	0.604	neutral	N	0.43048975	None	None	N
Y/I	0.78	likely_pathogenic	0.7637	pathogenic	-0.983	Destabilizing	0.329	N	0.611	neutral	None	None	None	None	N
Y/K	0.9945	likely_pathogenic	0.9943	pathogenic	-1.964	Destabilizing	0.936	D	0.761	deleterious	None	None	None	None	N
Y/L	0.5322	ambiguous	0.4822	ambiguous	-0.983	Destabilizing	0.003	N	0.497	neutral	None	None	None	None	N
Y/M	0.8137	likely_pathogenic	0.7909	pathogenic	-0.855	Destabilizing	0.893	D	0.732	prob.delet.	None	None	None	None	N
Y/N	0.9541	likely_pathogenic	0.9536	pathogenic	-2.919	Highly Destabilizing	0.975	D	0.791	deleterious	N	0.43048975	None	None	N
Y/P	0.9987	likely_pathogenic	0.9988	pathogenic	-1.49	Destabilizing	0.981	D	0.825	deleterious	None	None	None	None	N
Y/Q	0.9947	likely_pathogenic	0.9944	pathogenic	-2.498	Highly Destabilizing	0.981	D	0.737	prob.delet.	None	None	None	None	N
Y/R	0.9894	likely_pathogenic	0.9888	pathogenic	-2.179	Highly Destabilizing	0.981	D	0.787	deleterious	None	None	None	None	N
Y/S	0.9677	likely_pathogenic	0.9662	pathogenic	-3.165	Highly Destabilizing	0.784	D	0.691	prob.neutral	N	0.43048975	None	None	N
Y/T	0.9796	likely_pathogenic	0.9799	pathogenic	-2.777	Highly Destabilizing	0.828	D	0.688	prob.neutral	None	None	None	None	N
Y/V	0.7693	likely_pathogenic	0.767	pathogenic	-1.49	Destabilizing	0.329	N	0.619	neutral	None	None	None	None	N
Y/W	0.8365	likely_pathogenic	0.8433	pathogenic	-0.144	Destabilizing	0.981	D	0.599	neutral	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.