TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4019	12280;12281;12282	chr2:178741178;178741177;178741176	chr2:179605905;179605904;179605903
N2AB	3702	11329;11330;11331	chr2:178741178;178741177;178741176	chr2:179605905;179605904;179605903
N2A	None	None	chr2:None	chr2:None
N2B	3656	11191;11192;11193	chr2:178741178;178741177;178741176	chr2:179605905;179605904;179605903
Novex-1	3781	11566;11567;11568	chr2:178741178;178741177;178741176	chr2:179605905;179605904;179605903
Novex-2	3848	11767;11768;11769	chr2:178741178;178741177;178741176	chr2:179605905;179605904;179605903
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-28
• Domain position: 82
• Structural Position: 165
• Q(SASA): 0.413
• 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/K	None	None	None	N	0.198	0.113	None	gnomAD-4.0.0	4.77686E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	2.41313E-04	2.85791E-06	0	3.02444E-05

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	0.144	likely_benign	0.1607	benign	-0.523	Destabilizing	None	N	0.208	neutral	D	0.574708127	None	None	I
E/C	0.8339	likely_pathogenic	0.8199	pathogenic	-0.011	Destabilizing	0.824	D	0.537	neutral	None	None	None	None	I
E/D	0.2596	likely_benign	0.241	benign	-0.515	Destabilizing	0.117	N	0.3	neutral	D	0.583705652	None	None	I
E/F	0.6827	likely_pathogenic	0.6613	pathogenic	-0.444	Destabilizing	0.555	D	0.543	neutral	None	None	None	None	I
E/G	0.1972	likely_benign	0.1903	benign	-0.739	Destabilizing	None	N	0.307	neutral	D	0.58484413	None	None	I
E/H	0.496	ambiguous	0.4853	ambiguous	-0.377	Destabilizing	0.38	N	0.453	neutral	None	None	None	None	I
E/I	0.3427	ambiguous	0.3402	ambiguous	0.019	Stabilizing	0.38	N	0.553	neutral	None	None	None	None	I
E/K	0.1299	likely_benign	0.1344	benign	0.229	Stabilizing	None	N	0.198	neutral	N	0.507653416	None	None	I
E/L	0.4788	ambiguous	0.4803	ambiguous	0.019	Stabilizing	0.081	N	0.541	neutral	None	None	None	None	I
E/M	0.4322	ambiguous	0.4333	ambiguous	0.263	Stabilizing	0.824	D	0.521	neutral	None	None	None	None	I
E/N	0.3398	likely_benign	0.3306	benign	-0.069	Destabilizing	0.149	N	0.399	neutral	None	None	None	None	I
E/P	0.9085	likely_pathogenic	0.8764	pathogenic	-0.141	Destabilizing	0.555	D	0.457	neutral	None	None	None	None	I
E/Q	0.1291	likely_benign	0.1311	benign	-0.053	Destabilizing	0.001	N	0.189	neutral	N	0.507601806	None	None	I
E/R	0.2509	likely_benign	0.2461	benign	0.383	Stabilizing	0.081	N	0.404	neutral	None	None	None	None	I
E/S	0.1953	likely_benign	0.2005	benign	-0.248	Destabilizing	0.035	N	0.303	neutral	None	None	None	None	I
E/T	0.2052	likely_benign	0.2057	benign	-0.074	Destabilizing	0.002	N	0.253	neutral	None	None	None	None	I
E/V	0.2039	likely_benign	0.2023	benign	-0.141	Destabilizing	0.062	N	0.531	neutral	D	0.542278259	None	None	I
E/W	0.9025	likely_pathogenic	0.878	pathogenic	-0.281	Destabilizing	0.935	D	0.58	neutral	None	None	None	None	I
E/Y	0.6184	likely_pathogenic	0.5996	pathogenic	-0.192	Destabilizing	0.555	D	0.533	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.