TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29970	90133;90134;90135	chr2:178552992;178552991;178552990	chr2:179417719;179417718;179417717
N2AB	28329	85210;85211;85212	chr2:178552992;178552991;178552990	chr2:179417719;179417718;179417717
N2A	27402	82429;82430;82431	chr2:178552992;178552991;178552990	chr2:179417719;179417718;179417717
N2B	20905	62938;62939;62940	chr2:178552992;178552991;178552990	chr2:179417719;179417718;179417717
Novex-1	21030	63313;63314;63315	chr2:178552992;178552991;178552990	chr2:179417719;179417718;179417717
Novex-2	21097	63514;63515;63516	chr2:178552992;178552991;178552990	chr2:179417719;179417718;179417717
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: Fn3-106
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0519
• 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	0.722	D	0.609	0.436	0.73655689342	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	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	0.7555	likely_pathogenic	0.7123	pathogenic	-3.173	Highly Destabilizing	0.415	N	0.647	neutral	None	None	None	None	N
I/C	0.9468	likely_pathogenic	0.9397	pathogenic	-2.2	Highly Destabilizing	0.996	D	0.785	deleterious	None	None	None	None	N
I/D	0.9988	likely_pathogenic	0.9987	pathogenic	-3.802	Highly Destabilizing	0.987	D	0.869	deleterious	None	None	None	None	N
I/E	0.9952	likely_pathogenic	0.9947	pathogenic	-3.472	Highly Destabilizing	0.961	D	0.847	deleterious	None	None	None	None	N
I/F	0.7436	likely_pathogenic	0.6796	pathogenic	-1.908	Destabilizing	0.901	D	0.651	neutral	N	0.517200351	None	None	N
I/G	0.9853	likely_pathogenic	0.983	pathogenic	-3.783	Highly Destabilizing	0.961	D	0.813	deleterious	None	None	None	None	N
I/H	0.9959	likely_pathogenic	0.9952	pathogenic	-3.342	Highly Destabilizing	0.996	D	0.873	deleterious	None	None	None	None	N
I/K	0.9907	likely_pathogenic	0.9896	pathogenic	-2.539	Highly Destabilizing	0.961	D	0.851	deleterious	None	None	None	None	N
I/L	0.2456	likely_benign	0.2231	benign	-1.319	Destabilizing	0.19	N	0.316	neutral	N	0.480678136	None	None	N
I/M	0.3046	likely_benign	0.2738	benign	-1.407	Destabilizing	0.901	D	0.637	neutral	N	0.516946861	None	None	N
I/N	0.9855	likely_pathogenic	0.9852	pathogenic	-3.267	Highly Destabilizing	0.983	D	0.881	deleterious	D	0.535558095	None	None	N
I/P	0.9876	likely_pathogenic	0.9869	pathogenic	-1.931	Destabilizing	0.987	D	0.874	deleterious	None	None	None	None	N
I/Q	0.9916	likely_pathogenic	0.9907	pathogenic	-2.915	Highly Destabilizing	0.987	D	0.885	deleterious	None	None	None	None	N
I/R	0.9848	likely_pathogenic	0.983	pathogenic	-2.492	Highly Destabilizing	0.961	D	0.879	deleterious	None	None	None	None	N
I/S	0.9498	likely_pathogenic	0.9444	pathogenic	-3.819	Highly Destabilizing	0.901	D	0.771	deleterious	D	0.535558095	None	None	N
I/T	0.6309	likely_pathogenic	0.6036	pathogenic	-3.329	Highly Destabilizing	0.722	D	0.609	neutral	D	0.535304606	None	None	N
I/V	0.0755	likely_benign	0.0699	benign	-1.931	Destabilizing	0.001	N	0.203	neutral	N	0.389413053	None	None	N
I/W	0.9945	likely_pathogenic	0.9933	pathogenic	-2.283	Highly Destabilizing	0.996	D	0.859	deleterious	None	None	None	None	N
I/Y	0.9837	likely_pathogenic	0.9797	pathogenic	-2.137	Highly Destabilizing	0.961	D	0.747	deleterious	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.