TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17007	51244;51245;51246	chr2:178611110;178611109;178611108	chr2:179475837;179475836;179475835
N2AB	15366	46321;46322;46323	chr2:178611110;178611109;178611108	chr2:179475837;179475836;179475835
N2A	14439	43540;43541;43542	chr2:178611110;178611109;178611108	chr2:179475837;179475836;179475835
N2B	7942	24049;24050;24051	chr2:178611110;178611109;178611108	chr2:179475837;179475836;179475835
Novex-1	8067	24424;24425;24426	chr2:178611110;178611109;178611108	chr2:179475837;179475836;179475835
Novex-2	8134	24625;24626;24627	chr2:178611110;178611109;178611108	chr2:179475837;179475836;179475835
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-111
• Domain position: 53
• Structural Position: 131
• Q(SASA): 0.8018
• Predicted PPI site: I

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	None	None	0.523	N	0.159	0.139	0.0986583533028	gnomAD-4.0.0	1.59322E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86205E-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	0.2133	likely_benign	0.207	benign	0.209	Stabilizing	0.228	N	0.24	neutral	None	None	None	None	I
H/C	0.19	likely_benign	0.1665	benign	0.319	Stabilizing	0.94	D	0.258	neutral	None	None	None	None	I
H/D	0.1823	likely_benign	0.1614	benign	-0.291	Destabilizing	0.523	D	0.286	neutral	N	0.390421016	None	None	I
H/E	0.281	likely_benign	0.2792	benign	-0.277	Destabilizing	0.375	N	0.115	neutral	None	None	None	None	I
H/F	0.2411	likely_benign	0.2561	benign	0.803	Stabilizing	0.129	N	0.249	neutral	None	None	None	None	I
H/G	0.238	likely_benign	0.2159	benign	-0.013	Destabilizing	0.593	D	0.281	neutral	None	None	None	None	I
H/I	0.2604	likely_benign	0.2443	benign	0.763	Stabilizing	0.004	N	0.182	neutral	None	None	None	None	I
H/K	0.2592	likely_benign	0.2456	benign	0.109	Stabilizing	0.418	N	0.3	neutral	None	None	None	None	I
H/L	0.124	likely_benign	0.115	benign	0.763	Stabilizing	0.047	N	0.261	neutral	N	0.436329209	None	None	I
H/M	0.3682	ambiguous	0.3544	ambiguous	0.432	Stabilizing	0.836	D	0.271	neutral	None	None	None	None	I
H/N	0.0845	likely_benign	0.0792	benign	-0.091	Destabilizing	0.523	D	0.151	neutral	N	0.400529011	None	None	I
H/P	0.1342	likely_benign	0.1223	benign	0.601	Stabilizing	0.921	D	0.356	neutral	N	0.420048176	None	None	I
H/Q	0.1764	likely_benign	0.1735	benign	-0.003	Destabilizing	0.523	D	0.187	neutral	N	0.435294528	None	None	I
H/R	0.1235	likely_benign	0.1159	benign	-0.319	Destabilizing	0.523	D	0.159	neutral	N	0.442839577	None	None	I
H/S	0.1741	likely_benign	0.167	benign	None	Stabilizing	0.228	N	0.269	neutral	None	None	None	None	I
H/T	0.2076	likely_benign	0.2007	benign	0.11	Stabilizing	0.593	D	0.287	neutral	None	None	None	None	I
H/V	0.217	likely_benign	0.2044	benign	0.601	Stabilizing	0.061	N	0.278	neutral	None	None	None	None	I
H/W	0.4172	ambiguous	0.3828	ambiguous	0.734	Stabilizing	0.836	D	0.259	neutral	None	None	None	None	I
H/Y	0.0838	likely_benign	0.086	benign	0.951	Stabilizing	None	N	0.083	neutral	N	0.431734083	None	None	I

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.