TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31048	93367;93368;93369	chr2:178548484;178548483;178548482	chr2:179413211;179413210;179413209
N2AB	29407	88444;88445;88446	chr2:178548484;178548483;178548482	chr2:179413211;179413210;179413209
N2A	28480	85663;85664;85665	chr2:178548484;178548483;178548482	chr2:179413211;179413210;179413209
N2B	21983	66172;66173;66174	chr2:178548484;178548483;178548482	chr2:179413211;179413210;179413209
Novex-1	22108	66547;66548;66549	chr2:178548484;178548483;178548482	chr2:179413211;179413210;179413209
Novex-2	22175	66748;66749;66750	chr2:178548484;178548483;178548482	chr2:179413211;179413210;179413209
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-114
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.2102
• 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
I/F	None	None	0.942	D	0.745	0.426	0.463758542814	gnomAD-4.0.0	6.84184E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99449E-07	0	0
I/V	None	None	0.006	N	0.243	0.084	0.507331908393	gnomAD-4.0.0	6.84184E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99449E-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	0.9728	likely_pathogenic	0.9664	pathogenic	-2.462	Highly Destabilizing	0.754	D	0.691	prob.neutral	None	None	None	None	I
I/C	0.9658	likely_pathogenic	0.9576	pathogenic	-1.263	Destabilizing	0.994	D	0.733	prob.delet.	None	None	None	None	I
I/D	0.9983	likely_pathogenic	0.997	pathogenic	-2.585	Highly Destabilizing	0.993	D	0.826	deleterious	None	None	None	None	I
I/E	0.9948	likely_pathogenic	0.9921	pathogenic	-2.499	Highly Destabilizing	0.978	D	0.823	deleterious	None	None	None	None	I
I/F	0.8708	likely_pathogenic	0.8616	pathogenic	-1.666	Destabilizing	0.942	D	0.745	deleterious	D	0.529145179	None	None	I
I/G	0.9923	likely_pathogenic	0.9893	pathogenic	-2.866	Highly Destabilizing	0.978	D	0.818	deleterious	None	None	None	None	I
I/H	0.994	likely_pathogenic	0.9914	pathogenic	-2.251	Highly Destabilizing	0.998	D	0.793	deleterious	None	None	None	None	I
I/K	0.9885	likely_pathogenic	0.9838	pathogenic	-1.917	Destabilizing	0.978	D	0.823	deleterious	None	None	None	None	I
I/L	0.3847	ambiguous	0.371	ambiguous	-1.338	Destabilizing	0.294	N	0.479	neutral	N	0.497531798	None	None	I
I/M	0.5624	ambiguous	0.5442	ambiguous	-0.841	Destabilizing	0.942	D	0.713	prob.delet.	D	0.523944619	None	None	I
I/N	0.9551	likely_pathogenic	0.9278	pathogenic	-1.811	Destabilizing	0.99	D	0.828	deleterious	D	0.559192078	None	None	I
I/P	0.9644	likely_pathogenic	0.9427	pathogenic	-1.691	Destabilizing	0.993	D	0.833	deleterious	None	None	None	None	I
I/Q	0.9895	likely_pathogenic	0.986	pathogenic	-1.91	Destabilizing	0.993	D	0.825	deleterious	None	None	None	None	I
I/R	0.9861	likely_pathogenic	0.9808	pathogenic	-1.307	Destabilizing	0.978	D	0.825	deleterious	None	None	None	None	I
I/S	0.97	likely_pathogenic	0.958	pathogenic	-2.363	Highly Destabilizing	0.942	D	0.793	deleterious	D	0.547075304	None	None	I
I/T	0.9481	likely_pathogenic	0.9374	pathogenic	-2.174	Highly Destabilizing	0.822	D	0.778	deleterious	D	0.526502287	None	None	I
I/V	0.1188	likely_benign	0.122	benign	-1.691	Destabilizing	0.006	N	0.243	neutral	N	0.463265811	None	None	I
I/W	0.9966	likely_pathogenic	0.996	pathogenic	-1.958	Destabilizing	0.998	D	0.747	deleterious	None	None	None	None	I
I/Y	0.9812	likely_pathogenic	0.9761	pathogenic	-1.77	Destabilizing	0.978	D	0.77	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.