TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24340	73243;73244;73245	chr2:178573114;178573113;178573112	chr2:179437841;179437840;179437839
N2AB	22699	68320;68321;68322	chr2:178573114;178573113;178573112	chr2:179437841;179437840;179437839
N2A	21772	65539;65540;65541	chr2:178573114;178573113;178573112	chr2:179437841;179437840;179437839
N2B	15275	46048;46049;46050	chr2:178573114;178573113;178573112	chr2:179437841;179437840;179437839
Novex-1	15400	46423;46424;46425	chr2:178573114;178573113;178573112	chr2:179437841;179437840;179437839
Novex-2	15467	46624;46625;46626	chr2:178573114;178573113;178573112	chr2:179437841;179437840;179437839
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: Fn3-65
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.1674
• 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	0.822	N	0.773	0.418	0.694220761729	gnomAD-4.0.0	1.59224E-06	None	None	None	None	N	None	0	2.28739E-05	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	0.9137	likely_pathogenic	0.8982	pathogenic	-2.79	Highly Destabilizing	0.019	N	0.499	neutral	None	None	None	None	N
I/C	0.9342	likely_pathogenic	0.9274	pathogenic	-3.025	Highly Destabilizing	0.994	D	0.778	deleterious	None	None	None	None	N
I/D	0.9994	likely_pathogenic	0.9993	pathogenic	-2.631	Highly Destabilizing	0.978	D	0.838	deleterious	None	None	None	None	N
I/E	0.9979	likely_pathogenic	0.9981	pathogenic	-2.418	Highly Destabilizing	0.956	D	0.823	deleterious	None	None	None	None	N
I/F	0.6558	likely_pathogenic	0.673	pathogenic	-1.899	Destabilizing	0.97	D	0.733	prob.delet.	N	0.486221037	None	None	N
I/G	0.9945	likely_pathogenic	0.9936	pathogenic	-3.306	Highly Destabilizing	0.915	D	0.777	deleterious	None	None	None	None	N
I/H	0.9952	likely_pathogenic	0.9948	pathogenic	-2.565	Highly Destabilizing	0.998	D	0.817	deleterious	None	None	None	None	N
I/K	0.9947	likely_pathogenic	0.9956	pathogenic	-2.176	Highly Destabilizing	0.956	D	0.825	deleterious	None	None	None	None	N
I/L	0.2537	likely_benign	0.2803	benign	-1.297	Destabilizing	0.294	N	0.449	neutral	N	0.493905644	None	None	N
I/M	0.3227	likely_benign	0.3693	ambiguous	-1.719	Destabilizing	0.97	D	0.684	prob.neutral	N	0.521060534	None	None	N
I/N	0.9895	likely_pathogenic	0.9879	pathogenic	-2.504	Highly Destabilizing	0.97	D	0.827	deleterious	N	0.511886616	None	None	N
I/P	0.9984	likely_pathogenic	0.9982	pathogenic	-1.777	Destabilizing	0.978	D	0.837	deleterious	None	None	None	None	N
I/Q	0.9938	likely_pathogenic	0.9942	pathogenic	-2.406	Highly Destabilizing	0.978	D	0.829	deleterious	None	None	None	None	N
I/R	0.9897	likely_pathogenic	0.9907	pathogenic	-1.857	Destabilizing	0.978	D	0.829	deleterious	None	None	None	None	N
I/S	0.9745	likely_pathogenic	0.9685	pathogenic	-3.364	Highly Destabilizing	0.698	D	0.759	deleterious	N	0.496237897	None	None	N
I/T	0.9523	likely_pathogenic	0.9504	pathogenic	-2.99	Highly Destabilizing	0.822	D	0.773	deleterious	N	0.511126148	None	None	N
I/V	0.0905	likely_benign	0.0924	benign	-1.777	Destabilizing	0.006	N	0.182	neutral	N	0.405270726	None	None	N
I/W	0.9945	likely_pathogenic	0.9947	pathogenic	-2.018	Highly Destabilizing	0.998	D	0.799	deleterious	None	None	None	None	N
I/Y	0.9717	likely_pathogenic	0.9712	pathogenic	-1.827	Destabilizing	0.993	D	0.796	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.