TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26216	78871;78872;78873	chr2:178567486;178567485;178567484	chr2:179432213;179432212;179432211
N2AB	24575	73948;73949;73950	chr2:178567486;178567485;178567484	chr2:179432213;179432212;179432211
N2A	23648	71167;71168;71169	chr2:178567486;178567485;178567484	chr2:179432213;179432212;179432211
N2B	17151	51676;51677;51678	chr2:178567486;178567485;178567484	chr2:179432213;179432212;179432211
Novex-1	17276	52051;52052;52053	chr2:178567486;178567485;178567484	chr2:179432213;179432212;179432211
Novex-2	17343	52252;52253;52254	chr2:178567486;178567485;178567484	chr2:179432213;179432212;179432211
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-137
• Domain position: 24
• Structural Position: 34
• Q(SASA): 0.351
• 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
D/V	None	None	0.684	N	0.624	0.415	0.54038131941	gnomAD-4.0.0	1.5929E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86054E-06	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
D/A	0.3705	ambiguous	0.3308	benign	-0.348	Destabilizing	0.309	N	0.562	neutral	N	0.489940698	None	None	N
D/C	0.8752	likely_pathogenic	0.8421	pathogenic	-0.204	Destabilizing	0.996	D	0.639	neutral	None	None	None	None	N
D/E	0.4724	ambiguous	0.4277	ambiguous	-0.731	Destabilizing	0.472	N	0.458	neutral	N	0.501464414	None	None	N
D/F	0.8277	likely_pathogenic	0.7902	pathogenic	-0.123	Destabilizing	0.984	D	0.664	neutral	None	None	None	None	N
D/G	0.4959	ambiguous	0.4453	ambiguous	-0.683	Destabilizing	0.003	N	0.257	neutral	N	0.501120484	None	None	N
D/H	0.6059	likely_pathogenic	0.5614	ambiguous	-0.578	Destabilizing	0.994	D	0.581	neutral	N	0.50023505	None	None	N
D/I	0.6289	likely_pathogenic	0.5944	pathogenic	0.525	Stabilizing	0.91	D	0.651	neutral	None	None	None	None	N
D/K	0.7868	likely_pathogenic	0.7383	pathogenic	-0.538	Destabilizing	0.742	D	0.559	neutral	None	None	None	None	N
D/L	0.6653	likely_pathogenic	0.6262	pathogenic	0.525	Stabilizing	0.742	D	0.625	neutral	None	None	None	None	N
D/M	0.8148	likely_pathogenic	0.7792	pathogenic	0.888	Stabilizing	0.996	D	0.645	neutral	None	None	None	None	N
D/N	0.2258	likely_benign	0.2037	benign	-0.823	Destabilizing	0.684	D	0.466	neutral	D	0.529709808	None	None	N
D/P	0.9705	likely_pathogenic	0.9633	pathogenic	0.26	Stabilizing	0.953	D	0.594	neutral	None	None	None	None	N
D/Q	0.7271	likely_pathogenic	0.6844	pathogenic	-0.676	Destabilizing	0.953	D	0.521	neutral	None	None	None	None	N
D/R	0.7835	likely_pathogenic	0.7447	pathogenic	-0.426	Destabilizing	0.953	D	0.622	neutral	None	None	None	None	N
D/S	0.2993	likely_benign	0.2718	benign	-1.048	Destabilizing	0.045	N	0.177	neutral	None	None	None	None	N
D/T	0.4971	ambiguous	0.4594	ambiguous	-0.787	Destabilizing	0.037	N	0.295	neutral	None	None	None	None	N
D/V	0.4205	ambiguous	0.39	ambiguous	0.26	Stabilizing	0.684	D	0.624	neutral	N	0.519436886	None	None	N
D/W	0.9613	likely_pathogenic	0.9512	pathogenic	-0.066	Destabilizing	0.996	D	0.692	prob.neutral	None	None	None	None	N
D/Y	0.4643	ambiguous	0.4238	ambiguous	0.059	Stabilizing	0.979	D	0.657	neutral	N	0.494290838	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.