TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6183	18772;18773;18774	chr2:178729706;178729705;178729704	chr2:179594433;179594432;179594431
N2AB	5866	17821;17822;17823	chr2:178729706;178729705;178729704	chr2:179594433;179594432;179594431
N2A	4939	15040;15041;15042	chr2:178729706;178729705;178729704	chr2:179594433;179594432;179594431
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: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-45
• Domain position: 79
• Structural Position: 162
• Q(SASA): 0.992
• 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
D/G	None	None	0.969	N	0.5	0.432	0.382087116544	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
D/N	None	None	0.939	N	0.449	0.265	0.456089687795	gnomAD-4.0.0	1.59139E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85863E-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	0.1164	likely_benign	0.1289	benign	0.006	Stabilizing	0.939	D	0.459	neutral	N	0.427372087	None	None	I
D/C	0.6014	likely_pathogenic	0.6609	pathogenic	0.139	Stabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	I
D/E	0.1079	likely_benign	0.1216	benign	-0.261	Destabilizing	0.049	N	0.351	neutral	N	0.410207691	None	None	I
D/F	0.4628	ambiguous	0.5271	ambiguous	-0.174	Destabilizing	0.998	D	0.627	neutral	None	None	None	None	I
D/G	0.1486	likely_benign	0.1672	benign	-0.109	Destabilizing	0.969	D	0.5	neutral	N	0.464967683	None	None	I
D/H	0.2217	likely_benign	0.258	benign	0.229	Stabilizing	0.998	D	0.501	neutral	D	0.534443624	None	None	I
D/I	0.2273	likely_benign	0.2616	benign	0.238	Stabilizing	0.993	D	0.627	neutral	None	None	None	None	I
D/K	0.2369	likely_benign	0.2761	benign	0.545	Stabilizing	0.91	D	0.473	neutral	None	None	None	None	I
D/L	0.2667	likely_benign	0.3058	benign	0.238	Stabilizing	0.986	D	0.596	neutral	None	None	None	None	I
D/M	0.4762	ambiguous	0.5262	ambiguous	0.215	Stabilizing	0.999	D	0.649	neutral	None	None	None	None	I
D/N	0.0994	likely_benign	0.1109	benign	0.409	Stabilizing	0.939	D	0.449	neutral	N	0.509950611	None	None	I
D/P	0.4912	ambiguous	0.5552	ambiguous	0.18	Stabilizing	0.993	D	0.495	neutral	None	None	None	None	I
D/Q	0.246	likely_benign	0.2828	benign	0.389	Stabilizing	0.973	D	0.441	neutral	None	None	None	None	I
D/R	0.2699	likely_benign	0.3134	benign	0.655	Stabilizing	0.986	D	0.551	neutral	None	None	None	None	I
D/S	0.1086	likely_benign	0.1211	benign	0.307	Stabilizing	0.953	D	0.435	neutral	None	None	None	None	I
D/T	0.1818	likely_benign	0.2116	benign	0.395	Stabilizing	0.986	D	0.464	neutral	None	None	None	None	I
D/V	0.1421	likely_benign	0.1595	benign	0.18	Stabilizing	0.991	D	0.579	neutral	N	0.495117231	None	None	I
D/W	0.8204	likely_pathogenic	0.856	pathogenic	-0.15	Destabilizing	0.999	D	0.716	prob.delet.	None	None	None	None	I
D/Y	0.2022	likely_benign	0.2355	benign	0.051	Stabilizing	0.997	D	0.627	neutral	D	0.534616982	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.