TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20427	61504;61505;61506	chr2:178590446;178590445;178590444	chr2:179455173;179455172;179455171
N2AB	18786	56581;56582;56583	chr2:178590446;178590445;178590444	chr2:179455173;179455172;179455171
N2A	17859	53800;53801;53802	chr2:178590446;178590445;178590444	chr2:179455173;179455172;179455171
N2B	11362	34309;34310;34311	chr2:178590446;178590445;178590444	chr2:179455173;179455172;179455171
Novex-1	11487	34684;34685;34686	chr2:178590446;178590445;178590444	chr2:179455173;179455172;179455171
Novex-2	11554	34885;34886;34887	chr2:178590446;178590445;178590444	chr2:179455173;179455172;179455171
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: Fn3-36
• Domain position: 57
• Structural Position: 77
• Q(SASA): 0.1902
• 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/S	rs2049964140	None	0.942	N	0.667	0.391	0.806085154697	gnomAD-4.0.0	4.10725E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.3985E-06	0	0
I/T	None	None	0.822	N	0.593	0.303	0.583710156576	gnomAD-4.0.0	6.84541E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9975E-07	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	0.9258	likely_pathogenic	0.9267	pathogenic	-2.007	Highly Destabilizing	0.754	D	0.485	neutral	None	None	None	None	N
I/C	0.9038	likely_pathogenic	0.9287	pathogenic	-1.048	Destabilizing	0.994	D	0.701	prob.neutral	None	None	None	None	N
I/D	0.9906	likely_pathogenic	0.9909	pathogenic	-2.282	Highly Destabilizing	0.993	D	0.753	deleterious	None	None	None	None	N
I/E	0.9691	likely_pathogenic	0.9694	pathogenic	-2.016	Highly Destabilizing	0.978	D	0.733	prob.delet.	None	None	None	None	N
I/F	0.6573	likely_pathogenic	0.6531	pathogenic	-1.127	Destabilizing	0.942	D	0.591	neutral	N	0.477698661	None	None	N
I/G	0.9824	likely_pathogenic	0.9827	pathogenic	-2.57	Highly Destabilizing	0.978	D	0.719	prob.delet.	None	None	None	None	N
I/H	0.9492	likely_pathogenic	0.9578	pathogenic	-2.185	Highly Destabilizing	0.998	D	0.751	deleterious	None	None	None	None	N
I/K	0.9342	likely_pathogenic	0.9398	pathogenic	-1.373	Destabilizing	0.978	D	0.736	prob.delet.	None	None	None	None	N
I/L	0.2374	likely_benign	0.248	benign	-0.371	Destabilizing	0.294	N	0.399	neutral	N	0.49764217	None	None	N
I/M	0.3731	ambiguous	0.3916	ambiguous	-0.308	Destabilizing	0.942	D	0.599	neutral	N	0.473090305	None	None	N
I/N	0.8802	likely_pathogenic	0.8951	pathogenic	-1.842	Destabilizing	0.99	D	0.759	deleterious	N	0.521231105	None	None	N
I/P	0.9582	likely_pathogenic	0.9557	pathogenic	-0.898	Destabilizing	0.993	D	0.757	deleterious	None	None	None	None	N
I/Q	0.9105	likely_pathogenic	0.9226	pathogenic	-1.6	Destabilizing	0.993	D	0.758	deleterious	None	None	None	None	N
I/R	0.9075	likely_pathogenic	0.9168	pathogenic	-1.343	Destabilizing	0.978	D	0.757	deleterious	None	None	None	None	N
I/S	0.905	likely_pathogenic	0.9082	pathogenic	-2.491	Highly Destabilizing	0.942	D	0.667	neutral	N	0.506645655	None	None	N
I/T	0.9014	likely_pathogenic	0.9138	pathogenic	-2.07	Highly Destabilizing	0.822	D	0.593	neutral	N	0.498311386	None	None	N
I/V	0.1941	likely_benign	0.223	benign	-0.898	Destabilizing	0.006	N	0.235	neutral	N	0.468186054	None	None	N
I/W	0.971	likely_pathogenic	0.9727	pathogenic	-1.576	Destabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	N
I/Y	0.9333	likely_pathogenic	0.935	pathogenic	-1.189	Destabilizing	0.978	D	0.701	prob.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.