TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35147	105664;105665;105666	chr2:178531176;178531175;178531174	chr2:179395903;179395902;179395901
N2AB	33506	100741;100742;100743	chr2:178531176;178531175;178531174	chr2:179395903;179395902;179395901
N2A	32579	97960;97961;97962	chr2:178531176;178531175;178531174	chr2:179395903;179395902;179395901
N2B	26082	78469;78470;78471	chr2:178531176;178531175;178531174	chr2:179395903;179395902;179395901
Novex-1	26207	78844;78845;78846	chr2:178531176;178531175;178531174	chr2:179395903;179395902;179395901
Novex-2	26274	79045;79046;79047	chr2:178531176;178531175;178531174	chr2:179395903;179395902;179395901
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: Ig-164
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.557
• 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/S	None	None	0.961	N	0.592	0.272	0.198526703765	gnomAD-4.0.0	6.84137E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99394E-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
R/A	0.4603	ambiguous	0.4886	ambiguous	-0.439	Destabilizing	0.97	D	0.594	neutral	None	None	None	None	N
R/C	0.2073	likely_benign	0.1991	benign	-0.416	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
R/D	0.8525	likely_pathogenic	0.8576	pathogenic	0.008	Stabilizing	0.996	D	0.641	neutral	None	None	None	None	N
R/E	0.5036	ambiguous	0.5343	ambiguous	0.09	Stabilizing	0.97	D	0.601	neutral	None	None	None	None	N
R/F	0.5975	likely_pathogenic	0.6139	pathogenic	-0.55	Destabilizing	0.999	D	0.688	prob.neutral	None	None	None	None	N
R/G	0.4134	ambiguous	0.4312	ambiguous	-0.681	Destabilizing	0.98	D	0.599	neutral	N	0.497015959	None	None	N
R/H	0.1185	likely_benign	0.1195	benign	-1.09	Destabilizing	0.999	D	0.648	neutral	None	None	None	None	N
R/I	0.256	likely_benign	0.2853	benign	0.183	Stabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	N
R/K	0.1205	likely_benign	0.1222	benign	-0.414	Destabilizing	0.122	N	0.333	neutral	N	0.478679902	None	None	N
R/L	0.2831	likely_benign	0.3001	benign	0.183	Stabilizing	0.985	D	0.599	neutral	None	None	None	None	N
R/M	0.3388	likely_benign	0.3543	ambiguous	-0.104	Destabilizing	1.0	D	0.666	neutral	N	0.467301909	None	None	N
R/N	0.6816	likely_pathogenic	0.6891	pathogenic	0.049	Stabilizing	0.996	D	0.632	neutral	None	None	None	None	N
R/P	0.9358	likely_pathogenic	0.9386	pathogenic	-0.003	Destabilizing	0.999	D	0.678	prob.neutral	None	None	None	None	N
R/Q	0.1218	likely_benign	0.1256	benign	-0.155	Destabilizing	0.991	D	0.666	neutral	None	None	None	None	N
R/S	0.4765	ambiguous	0.505	ambiguous	-0.572	Destabilizing	0.961	D	0.592	neutral	N	0.496708302	None	None	N
R/T	0.2329	likely_benign	0.2481	benign	-0.335	Destabilizing	0.98	D	0.621	neutral	N	0.453722742	None	None	N
R/V	0.3232	likely_benign	0.3431	ambiguous	-0.003	Destabilizing	0.996	D	0.681	prob.neutral	None	None	None	None	N
R/W	0.2336	likely_benign	0.2266	benign	-0.388	Destabilizing	1.0	D	0.672	neutral	N	0.497269448	None	None	N
R/Y	0.4753	ambiguous	0.4707	ambiguous	-0.028	Destabilizing	0.999	D	0.68	prob.neutral	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.