TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16965	51118;51119;51120	chr2:178611236;178611235;178611234	chr2:179475963;179475962;179475961
N2AB	15324	46195;46196;46197	chr2:178611236;178611235;178611234	chr2:179475963;179475962;179475961
N2A	14397	43414;43415;43416	chr2:178611236;178611235;178611234	chr2:179475963;179475962;179475961
N2B	7900	23923;23924;23925	chr2:178611236;178611235;178611234	chr2:179475963;179475962;179475961
Novex-1	8025	24298;24299;24300	chr2:178611236;178611235;178611234	chr2:179475963;179475962;179475961
Novex-2	8092	24499;24500;24501	chr2:178611236;178611235;178611234	chr2:179475963;179475962;179475961
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-111
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.493
• 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
I/M	None	None	0.317	N	0.369	0.045	0.510172456258	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

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
I/A	0.2616	likely_benign	0.2292	benign	-1.161	Destabilizing	0.035	N	0.338	neutral	None	None	None	None	I
I/C	0.7142	likely_pathogenic	0.6639	pathogenic	-0.776	Destabilizing	0.824	D	0.381	neutral	None	None	None	None	I
I/D	0.6961	likely_pathogenic	0.644	pathogenic	-0.647	Destabilizing	0.555	D	0.402	neutral	None	None	None	None	I
I/E	0.525	ambiguous	0.4795	ambiguous	-0.67	Destabilizing	0.555	D	0.395	neutral	None	None	None	None	I
I/F	0.2366	likely_benign	0.2051	benign	-0.781	Destabilizing	0.317	N	0.317	neutral	N	0.510483256	None	None	I
I/G	0.7198	likely_pathogenic	0.6622	pathogenic	-1.428	Destabilizing	0.262	N	0.391	neutral	None	None	None	None	I
I/H	0.564	ambiguous	0.4842	ambiguous	-0.55	Destabilizing	0.935	D	0.369	neutral	None	None	None	None	I
I/K	0.4612	ambiguous	0.4111	ambiguous	-0.837	Destabilizing	0.555	D	0.395	neutral	None	None	None	None	I
I/L	0.1487	likely_benign	0.1284	benign	-0.526	Destabilizing	0.005	N	0.22	neutral	N	0.464965916	None	None	I
I/M	0.1303	likely_benign	0.1094	benign	-0.53	Destabilizing	0.317	N	0.369	neutral	N	0.490068566	None	None	I
I/N	0.3172	likely_benign	0.2796	benign	-0.669	Destabilizing	0.741	D	0.399	neutral	N	0.474219744	None	None	I
I/P	0.8117	likely_pathogenic	0.7624	pathogenic	-0.705	Destabilizing	0.555	D	0.408	neutral	None	None	None	None	I
I/Q	0.4895	ambiguous	0.4331	ambiguous	-0.838	Destabilizing	0.791	D	0.392	neutral	None	None	None	None	I
I/R	0.3815	ambiguous	0.3333	benign	-0.241	Destabilizing	0.555	D	0.394	neutral	None	None	None	None	I
I/S	0.2774	likely_benign	0.2457	benign	-1.198	Destabilizing	0.117	N	0.369	neutral	N	0.445296968	None	None	I
I/T	0.1158	likely_benign	0.1021	benign	-1.105	Destabilizing	0.062	N	0.311	neutral	N	0.397851736	None	None	I
I/V	0.0635	likely_benign	0.0625	benign	-0.705	Destabilizing	None	N	0.098	neutral	N	0.345602821	None	None	I
I/W	0.8558	likely_pathogenic	0.8176	pathogenic	-0.827	Destabilizing	0.935	D	0.454	neutral	None	None	None	None	I
I/Y	0.5801	likely_pathogenic	0.5394	ambiguous	-0.609	Destabilizing	0.555	D	0.401	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.