TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28589	85990;85991;85992	chr2:178560367;178560366;178560365	chr2:179425094;179425093;179425092
N2AB	26948	81067;81068;81069	chr2:178560367;178560366;178560365	chr2:179425094;179425093;179425092
N2A	26021	78286;78287;78288	chr2:178560367;178560366;178560365	chr2:179425094;179425093;179425092
N2B	19524	58795;58796;58797	chr2:178560367;178560366;178560365	chr2:179425094;179425093;179425092
Novex-1	19649	59170;59171;59172	chr2:178560367;178560366;178560365	chr2:179425094;179425093;179425092
Novex-2	19716	59371;59372;59373	chr2:178560367;178560366;178560365	chr2:179425094;179425093;179425092
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Fn3-96
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.264
• 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
R/K	rs769856738	-1.17	0.122	N	0.267	0.183	0.170165803431	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
R/K	rs769856738	-1.17	0.122	N	0.267	0.183	0.170165803431	gnomAD-4.0.0	3.18304E-06	None	None	None	None	N	None	0	4.57331E-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
R/A	0.9206	likely_pathogenic	0.8779	pathogenic	-2.021	Highly Destabilizing	0.931	D	0.617	neutral	None	None	None	None	N
R/C	0.3544	ambiguous	0.2666	benign	-1.911	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
R/D	0.9889	likely_pathogenic	0.9834	pathogenic	-1.329	Destabilizing	0.996	D	0.72	prob.delet.	None	None	None	None	N
R/E	0.883	likely_pathogenic	0.8333	pathogenic	-1.085	Destabilizing	0.97	D	0.641	neutral	None	None	None	None	N
R/F	0.8874	likely_pathogenic	0.8484	pathogenic	-1.068	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
R/G	0.8252	likely_pathogenic	0.7568	pathogenic	-2.378	Highly Destabilizing	0.98	D	0.66	neutral	N	0.478356997	None	None	N
R/H	0.2475	likely_benign	0.191	benign	-1.781	Destabilizing	0.999	D	0.662	neutral	None	None	None	None	N
R/I	0.7721	likely_pathogenic	0.6941	pathogenic	-0.962	Destabilizing	0.999	D	0.75	deleterious	None	None	None	None	N
R/K	0.1283	likely_benign	0.1145	benign	-1.097	Destabilizing	0.122	N	0.267	neutral	N	0.398864829	None	None	N
R/L	0.6795	likely_pathogenic	0.5881	pathogenic	-0.962	Destabilizing	0.985	D	0.66	neutral	None	None	None	None	N
R/M	0.6621	likely_pathogenic	0.5865	pathogenic	-1.497	Destabilizing	1.0	D	0.702	prob.neutral	N	0.511880903	None	None	N
R/N	0.9624	likely_pathogenic	0.9427	pathogenic	-1.564	Destabilizing	0.985	D	0.653	neutral	None	None	None	None	N
R/P	0.9963	likely_pathogenic	0.9942	pathogenic	-1.307	Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
R/Q	0.2379	likely_benign	0.189	benign	-1.351	Destabilizing	0.97	D	0.691	prob.neutral	None	None	None	None	N
R/S	0.948	likely_pathogenic	0.915	pathogenic	-2.38	Highly Destabilizing	0.961	D	0.635	neutral	N	0.468633306	None	None	N
R/T	0.872	likely_pathogenic	0.8047	pathogenic	-1.913	Destabilizing	0.98	D	0.627	neutral	N	0.473722188	None	None	N
R/V	0.8398	likely_pathogenic	0.7748	pathogenic	-1.307	Destabilizing	0.996	D	0.732	prob.delet.	None	None	None	None	N
R/W	0.4641	ambiguous	0.3784	ambiguous	-0.574	Destabilizing	1.0	D	0.735	prob.delet.	N	0.465453301	None	None	N
R/Y	0.7293	likely_pathogenic	0.655	pathogenic	-0.493	Destabilizing	0.999	D	0.742	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.