TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3403	10432;10433;10434	chr2:178759080;178759079;178759078	chr2:179623807;179623806;179623805
N2AB	3403	10432;10433;10434	chr2:178759080;178759079;178759078	chr2:179623807;179623806;179623805
N2A	3403	10432;10433;10434	chr2:178759080;178759079;178759078	chr2:179623807;179623806;179623805
N2B	3357	10294;10295;10296	chr2:178759080;178759079;178759078	chr2:179623807;179623806;179623805
Novex-1	3357	10294;10295;10296	chr2:178759080;178759079;178759078	chr2:179623807;179623806;179623805
Novex-2	3357	10294;10295;10296	chr2:178759080;178759079;178759078	chr2:179623807;179623806;179623805
Novex-3	3403	10432;10433;10434	chr2:178759080;178759079;178759078	chr2:179623807;179623806;179623805

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-24
• Domain position: 59
• Structural Position: 140
• Q(SASA): 0.0708
• 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/V	None	None	0.001	D	0.248	0.268	0.485634191555	gnomAD-4.0.0	3.18144E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41313E-04	0	0	3.02206E-05

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	0.8441	likely_pathogenic	0.8697	pathogenic	-2.812	Highly Destabilizing	0.25	N	0.706	prob.neutral	None	None	None	None	N
I/C	0.9679	likely_pathogenic	0.9723	pathogenic	-2.057	Highly Destabilizing	0.947	D	0.779	deleterious	None	None	None	None	N
I/D	0.9931	likely_pathogenic	0.9948	pathogenic	-3.5	Highly Destabilizing	0.826	D	0.888	deleterious	None	None	None	None	N
I/E	0.98	likely_pathogenic	0.9865	pathogenic	-3.19	Highly Destabilizing	0.826	D	0.891	deleterious	None	None	None	None	N
I/F	0.5249	ambiguous	0.5667	pathogenic	-1.685	Destabilizing	0.638	D	0.74	deleterious	D	0.665004251	None	None	N
I/G	0.9813	likely_pathogenic	0.9853	pathogenic	-3.429	Highly Destabilizing	0.826	D	0.892	deleterious	None	None	None	None	N
I/H	0.9816	likely_pathogenic	0.9854	pathogenic	-3.033	Highly Destabilizing	0.982	D	0.879	deleterious	None	None	None	None	N
I/K	0.961	likely_pathogenic	0.9705	pathogenic	-2.282	Highly Destabilizing	0.826	D	0.891	deleterious	None	None	None	None	N
I/L	0.2858	likely_benign	0.3099	benign	-0.971	Destabilizing	0.043	N	0.391	neutral	D	0.59853196	None	None	N
I/M	0.2407	likely_benign	0.235	benign	-1.019	Destabilizing	0.638	D	0.687	prob.neutral	D	0.714412396	None	None	N
I/N	0.9367	likely_pathogenic	0.9481	pathogenic	-2.911	Highly Destabilizing	0.916	D	0.897	deleterious	D	0.812455333	None	None	N
I/P	0.9911	likely_pathogenic	0.992	pathogenic	-1.573	Destabilizing	0.935	D	0.889	deleterious	None	None	None	None	N
I/Q	0.9725	likely_pathogenic	0.9804	pathogenic	-2.614	Highly Destabilizing	0.935	D	0.904	deleterious	None	None	None	None	N
I/R	0.9471	likely_pathogenic	0.9602	pathogenic	-2.189	Highly Destabilizing	0.826	D	0.905	deleterious	None	None	None	None	N
I/S	0.925	likely_pathogenic	0.9366	pathogenic	-3.542	Highly Destabilizing	0.638	D	0.857	deleterious	D	0.812455333	None	None	N
I/T	0.8242	likely_pathogenic	0.8562	pathogenic	-3.068	Highly Destabilizing	0.201	N	0.773	deleterious	D	0.730335682	None	None	N
I/V	0.1156	likely_benign	0.1467	benign	-1.573	Destabilizing	0.001	N	0.248	neutral	D	0.576957561	None	None	N
I/W	0.9796	likely_pathogenic	0.9767	pathogenic	-2.15	Highly Destabilizing	0.982	D	0.873	deleterious	None	None	None	None	N
I/Y	0.9256	likely_pathogenic	0.932	pathogenic	-1.882	Destabilizing	0.826	D	0.771	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.