TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5432	16519;16520;16521	chr2:178732882;178732881;178732880	chr2:179597609;179597608;179597607
N2AB	5115	15568;15569;15570	chr2:178732882;178732881;178732880	chr2:179597609;179597608;179597607
N2A	4188	12787;12788;12789	chr2:178732882;178732881;178732880	chr2:179597609;179597608;179597607
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-37
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.3179
• 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
T/R	None	None	0.997	D	0.705	0.397	0.856718553135	gnomAD-4.0.0	1.59238E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.88445E-05	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
T/A	0.0911	likely_benign	0.0877	benign	-0.684	Destabilizing	0.948	D	0.603	neutral	N	0.488165226	None	None	I
T/C	0.5253	ambiguous	0.5037	ambiguous	-0.547	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
T/D	0.5001	ambiguous	0.5052	ambiguous	-1.146	Destabilizing	0.983	D	0.648	neutral	None	None	None	None	I
T/E	0.3292	likely_benign	0.3474	ambiguous	-1.143	Destabilizing	0.611	D	0.413	neutral	None	None	None	None	I
T/F	0.2828	likely_benign	0.2849	benign	-0.871	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
T/G	0.2895	likely_benign	0.2713	benign	-0.932	Destabilizing	0.992	D	0.719	prob.delet.	None	None	None	None	I
T/H	0.3239	likely_benign	0.3261	benign	-1.329	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	I
T/I	0.224	likely_benign	0.2174	benign	-0.113	Destabilizing	0.998	D	0.714	prob.delet.	N	0.494966082	None	None	I
T/K	0.2938	likely_benign	0.2938	benign	-0.783	Destabilizing	0.989	D	0.643	neutral	D	0.525805498	None	None	I
T/L	0.1621	likely_benign	0.1589	benign	-0.113	Destabilizing	0.996	D	0.65	neutral	None	None	None	None	I
T/M	0.12	likely_benign	0.1178	benign	0.303	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
T/N	0.1916	likely_benign	0.1851	benign	-0.884	Destabilizing	0.998	D	0.665	neutral	None	None	None	None	I
T/P	0.8485	likely_pathogenic	0.8139	pathogenic	-0.272	Destabilizing	0.999	D	0.705	prob.neutral	D	0.54499966	None	None	I
T/Q	0.2386	likely_benign	0.2331	benign	-1.144	Destabilizing	0.998	D	0.705	prob.neutral	None	None	None	None	I
T/R	0.2036	likely_benign	0.2001	benign	-0.485	Destabilizing	0.997	D	0.705	prob.neutral	D	0.534638412	None	None	I
T/S	0.1046	likely_benign	0.1042	benign	-0.998	Destabilizing	0.775	D	0.349	neutral	N	0.472088443	None	None	I
T/V	0.1524	likely_benign	0.1505	benign	-0.272	Destabilizing	0.996	D	0.639	neutral	None	None	None	None	I
T/W	0.6323	likely_pathogenic	0.6304	pathogenic	-0.868	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	I
T/Y	0.386	ambiguous	0.3748	ambiguous	-0.577	Destabilizing	1.0	D	0.805	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.