TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14378	43357;43358;43359	chr2:178632999;178632998;178632997	chr2:179497726;179497725;179497724
N2AB	12737	38434;38435;38436	chr2:178632999;178632998;178632997	chr2:179497726;179497725;179497724
N2A	11810	35653;35654;35655	chr2:178632999;178632998;178632997	chr2:179497726;179497725;179497724
N2B	5313	16162;16163;16164	chr2:178632999;178632998;178632997	chr2:179497726;179497725;179497724
Novex-1	5438	16537;16538;16539	chr2:178632999;178632998;178632997	chr2:179497726;179497725;179497724
Novex-2	5505	16738;16739;16740	chr2:178632999;178632998;178632997	chr2:179497726;179497725;179497724
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-94
• Domain position: 60
• Structural Position: 141
• Q(SASA): 0.1764
• 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/Q	rs2059987336	None	0.052	N	0.254	0.052	0.0986583533028	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
H/Q	rs2059987336	None	0.052	N	0.254	0.052	0.0986583533028	gnomAD-4.0.0	6.57358E-06	None	None	None	None	N	None	2.4122E-05	0	None	0	0	None	0	0	0	0	0
H/R	rs878854307	None	0.026	N	0.217	0.106	0.0920862733494	gnomAD-4.0.0	1.59267E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86089E-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	0.5095	ambiguous	0.462	ambiguous	-0.451	Destabilizing	0.015	N	0.268	neutral	None	None	None	None	N
H/C	0.2284	likely_benign	0.2122	benign	0.102	Stabilizing	0.747	D	0.361	neutral	None	None	None	None	N
H/D	0.3745	ambiguous	0.3529	ambiguous	-0.567	Destabilizing	0.052	N	0.361	neutral	N	0.436169418	None	None	N
H/E	0.3909	ambiguous	0.368	ambiguous	-0.515	Destabilizing	0.029	N	0.199	neutral	None	None	None	None	N
H/F	0.3659	ambiguous	0.3337	benign	0.047	Stabilizing	0.007	N	0.293	neutral	None	None	None	None	N
H/G	0.403	ambiguous	0.3573	ambiguous	-0.752	Destabilizing	0.068	N	0.311	neutral	None	None	None	None	N
H/I	0.595	likely_pathogenic	0.5332	ambiguous	0.354	Stabilizing	0.035	N	0.42	neutral	None	None	None	None	N
H/K	0.2541	likely_benign	0.2328	benign	-0.368	Destabilizing	0.035	N	0.342	neutral	None	None	None	None	N
H/L	0.234	likely_benign	0.2112	benign	0.354	Stabilizing	0.006	N	0.287	neutral	N	0.431130499	None	None	N
H/M	0.7029	likely_pathogenic	0.6443	pathogenic	0.324	Stabilizing	0.204	N	0.335	neutral	None	None	None	None	N
H/N	0.1607	likely_benign	0.1554	benign	-0.29	Destabilizing	0.052	N	0.247	neutral	N	0.431996154	None	None	N
H/P	0.2607	likely_benign	0.2777	benign	0.107	Stabilizing	0.371	N	0.472	neutral	N	0.431674792	None	None	N
H/Q	0.2205	likely_benign	0.2026	benign	-0.149	Destabilizing	0.052	N	0.254	neutral	N	0.435944658	None	None	N
H/R	0.0987	likely_benign	0.0943	benign	-0.626	Destabilizing	0.026	N	0.217	neutral	N	0.418288309	None	None	N
H/S	0.3434	ambiguous	0.3149	benign	-0.33	Destabilizing	0.035	N	0.295	neutral	None	None	None	None	N
H/T	0.4723	ambiguous	0.4057	ambiguous	-0.191	Destabilizing	0.035	N	0.335	neutral	None	None	None	None	N
H/V	0.5144	ambiguous	0.4614	ambiguous	0.107	Stabilizing	0.015	N	0.333	neutral	None	None	None	None	N
H/W	0.3217	likely_benign	0.2904	benign	0.03	Stabilizing	0.204	N	0.351	neutral	None	None	None	None	N
H/Y	0.0663	likely_benign	0.0658	benign	0.402	Stabilizing	None	N	0.049	neutral	N	0.380097531	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.