TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7079	21460;21461;21462	chr2:178724024;178724023;178724022	chr2:179588751;179588750;179588749
N2AB	6762	20509;20510;20511	chr2:178724024;178724023;178724022	chr2:179588751;179588750;179588749
N2A	5835	17728;17729;17730	chr2:178724024;178724023;178724022	chr2:179588751;179588750;179588749
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-55
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.1406
• 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
H/R	rs781652689	None	0.042	N	0.431	0.105	0.0762999501168	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56251E-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
H/A	0.4505	ambiguous	0.3946	ambiguous	-1.355	Destabilizing	0.055	N	0.544	neutral	None	None	None	None	N
H/C	0.2397	likely_benign	0.2306	benign	-0.784	Destabilizing	0.958	D	0.689	prob.neutral	None	None	None	None	N
H/D	0.4573	ambiguous	0.4164	ambiguous	-1.078	Destabilizing	0.175	N	0.594	neutral	N	0.461274748	None	None	N
H/E	0.3713	ambiguous	0.3291	benign	-0.924	Destabilizing	0.055	N	0.353	neutral	None	None	None	None	N
H/F	0.391	ambiguous	0.3815	ambiguous	0.046	Stabilizing	0.124	N	0.664	neutral	None	None	None	None	N
H/G	0.4623	ambiguous	0.4138	ambiguous	-1.763	Destabilizing	0.104	N	0.581	neutral	None	None	None	None	N
H/I	0.4359	ambiguous	0.4456	ambiguous	-0.185	Destabilizing	0.124	N	0.682	prob.neutral	None	None	None	None	N
H/K	0.1723	likely_benign	0.1781	benign	-0.922	Destabilizing	0.002	N	0.361	neutral	None	None	None	None	N
H/L	0.1307	likely_benign	0.1293	benign	-0.185	Destabilizing	0.015	N	0.561	neutral	N	0.462729014	None	None	N
H/M	0.5433	ambiguous	0.543	ambiguous	-0.433	Destabilizing	0.009	N	0.553	neutral	None	None	None	None	N
H/N	0.2173	likely_benign	0.1941	benign	-1.313	Destabilizing	0.175	N	0.455	neutral	N	0.451070532	None	None	N
H/P	0.5758	likely_pathogenic	0.4864	ambiguous	-0.559	Destabilizing	0.301	N	0.682	prob.neutral	N	0.481847765	None	None	N
H/Q	0.1511	likely_benign	0.1352	benign	-0.981	Destabilizing	None	N	0.177	neutral	N	0.479199977	None	None	N
H/R	0.0782	likely_benign	0.0735	benign	-1.17	Destabilizing	0.042	N	0.431	neutral	N	0.444564541	None	None	N
H/S	0.3952	ambiguous	0.3382	benign	-1.493	Destabilizing	0.055	N	0.527	neutral	None	None	None	None	N
H/T	0.4932	ambiguous	0.4487	ambiguous	-1.22	Destabilizing	0.22	N	0.62	neutral	None	None	None	None	N
H/V	0.3778	ambiguous	0.3737	ambiguous	-0.559	Destabilizing	0.055	N	0.593	neutral	None	None	None	None	N
H/W	0.3624	ambiguous	0.3432	ambiguous	0.474	Stabilizing	0.958	D	0.665	neutral	None	None	None	None	N
H/Y	0.1245	likely_benign	0.1199	benign	0.503	Stabilizing	0.003	N	0.17	neutral	N	0.46051428	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.