TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28581	85966;85967;85968	chr2:178560391;178560390;178560389	chr2:179425118;179425117;179425116
N2AB	26940	81043;81044;81045	chr2:178560391;178560390;178560389	chr2:179425118;179425117;179425116
N2A	26013	78262;78263;78264	chr2:178560391;178560390;178560389	chr2:179425118;179425117;179425116
N2B	19516	58771;58772;58773	chr2:178560391;178560390;178560389	chr2:179425118;179425117;179425116
Novex-1	19641	59146;59147;59148	chr2:178560391;178560390;178560389	chr2:179425118;179425117;179425116
Novex-2	19708	59347;59348;59349	chr2:178560391;178560390;178560389	chr2:179425118;179425117;179425116
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-96
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.9283
• 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
E/Q	None	None	0.117	N	0.413	0.108	0.201204373187	gnomAD-4.0.0	1.59146E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8582E-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
E/A	0.1399	likely_benign	0.1238	benign	-0.147	Destabilizing	0.027	N	0.438	neutral	N	0.502301415	None	None	I
E/C	0.7348	likely_pathogenic	0.6797	pathogenic	0.127	Stabilizing	0.935	D	0.449	neutral	None	None	None	None	I
E/D	0.0873	likely_benign	0.0757	benign	-0.132	Destabilizing	None	N	0.112	neutral	N	0.48992955	None	None	I
E/F	0.6813	likely_pathogenic	0.6363	pathogenic	-0.174	Destabilizing	0.791	D	0.466	neutral	None	None	None	None	I
E/G	0.1672	likely_benign	0.1459	benign	-0.295	Destabilizing	0.052	N	0.471	neutral	N	0.518521661	None	None	I
E/H	0.4021	ambiguous	0.3477	ambiguous	0.16	Stabilizing	0.555	D	0.42	neutral	None	None	None	None	I
E/I	0.3281	likely_benign	0.2973	benign	0.19	Stabilizing	0.555	D	0.487	neutral	None	None	None	None	I
E/K	0.1414	likely_benign	0.1239	benign	0.567	Stabilizing	0.117	N	0.373	neutral	N	0.496932881	None	None	I
E/L	0.3524	ambiguous	0.3144	benign	0.19	Stabilizing	0.149	N	0.464	neutral	None	None	None	None	I
E/M	0.4249	ambiguous	0.3913	ambiguous	0.219	Stabilizing	0.935	D	0.463	neutral	None	None	None	None	I
E/N	0.1857	likely_benign	0.1535	benign	0.344	Stabilizing	0.081	N	0.384	neutral	None	None	None	None	I
E/P	0.2462	likely_benign	0.2108	benign	0.097	Stabilizing	0.001	N	0.305	neutral	None	None	None	None	I
E/Q	0.147	likely_benign	0.1387	benign	0.362	Stabilizing	0.117	N	0.413	neutral	N	0.469864755	None	None	I
E/R	0.224	likely_benign	0.209	benign	0.686	Stabilizing	0.38	N	0.388	neutral	None	None	None	None	I
E/S	0.1651	likely_benign	0.1416	benign	0.187	Stabilizing	0.003	N	0.096	neutral	None	None	None	None	I
E/T	0.214	likely_benign	0.1878	benign	0.313	Stabilizing	0.081	N	0.451	neutral	None	None	None	None	I
E/V	0.1908	likely_benign	0.1736	benign	0.097	Stabilizing	0.211	N	0.461	neutral	N	0.487234995	None	None	I
E/W	0.8568	likely_pathogenic	0.8193	pathogenic	-0.095	Destabilizing	0.935	D	0.549	neutral	None	None	None	None	I
E/Y	0.5141	ambiguous	0.4566	ambiguous	0.062	Stabilizing	0.791	D	0.478	neutral	None	None	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.