TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1023	3292;3293;3294	chr2:178782839;178782838;178782837	chr2:179647566;179647565;179647564
N2AB	1023	3292;3293;3294	chr2:178782839;178782838;178782837	chr2:179647566;179647565;179647564
N2A	1023	3292;3293;3294	chr2:178782839;178782838;178782837	chr2:179647566;179647565;179647564
N2B	977	3154;3155;3156	chr2:178782839;178782838;178782837	chr2:179647566;179647565;179647564
Novex-1	977	3154;3155;3156	chr2:178782839;178782838;178782837	chr2:179647566;179647565;179647564
Novex-2	977	3154;3155;3156	chr2:178782839;178782838;178782837	chr2:179647566;179647565;179647564
Novex-3	1023	3292;3293;3294	chr2:178782839;178782838;178782837	chr2:179647566;179647565;179647564

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-3
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.5376
• 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
T/I	None	None	0.997	N	0.669	0.389	0.536100336011	gnomAD-4.0.0	1.36872E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79879E-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
T/A	0.1239	likely_benign	0.1552	benign	-0.463	Destabilizing	0.898	D	0.485	neutral	N	0.482348844	None	None	I
T/C	0.6953	likely_pathogenic	0.7552	pathogenic	-0.392	Destabilizing	1.0	D	0.652	neutral	None	None	None	None	I
T/D	0.6204	likely_pathogenic	0.7314	pathogenic	0.137	Stabilizing	0.995	D	0.602	neutral	None	None	None	None	I
T/E	0.3998	ambiguous	0.5211	ambiguous	0.066	Stabilizing	0.995	D	0.604	neutral	None	None	None	None	I
T/F	0.4203	ambiguous	0.5267	ambiguous	-0.882	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	I
T/G	0.5018	ambiguous	0.5992	pathogenic	-0.605	Destabilizing	0.966	D	0.609	neutral	None	None	None	None	I
T/H	0.3687	ambiguous	0.4407	ambiguous	-0.889	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
T/I	0.3035	likely_benign	0.3915	ambiguous	-0.206	Destabilizing	0.997	D	0.669	neutral	N	0.457785789	None	None	I
T/K	0.2582	likely_benign	0.3375	benign	-0.456	Destabilizing	0.995	D	0.608	neutral	None	None	None	None	I
T/L	0.2096	likely_benign	0.2616	benign	-0.206	Destabilizing	0.983	D	0.601	neutral	None	None	None	None	I
T/M	0.109	likely_benign	0.1329	benign	-0.033	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	I
T/N	0.2012	likely_benign	0.2406	benign	-0.266	Destabilizing	0.993	D	0.64	neutral	N	0.47921575	None	None	I
T/P	0.5757	likely_pathogenic	0.7387	pathogenic	-0.263	Destabilizing	0.997	D	0.656	neutral	N	0.512815201	None	None	I
T/Q	0.2937	likely_benign	0.3606	ambiguous	-0.512	Destabilizing	0.998	D	0.663	neutral	None	None	None	None	I
T/R	0.2141	likely_benign	0.2996	benign	-0.164	Destabilizing	0.995	D	0.651	neutral	None	None	None	None	I
T/S	0.1408	likely_benign	0.1554	benign	-0.501	Destabilizing	0.362	N	0.333	neutral	N	0.406877454	None	None	I
T/V	0.2206	likely_benign	0.2652	benign	-0.263	Destabilizing	0.983	D	0.587	neutral	None	None	None	None	I
T/W	0.7894	likely_pathogenic	0.8588	pathogenic	-0.846	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
T/Y	0.5074	ambiguous	0.5993	pathogenic	-0.584	Destabilizing	0.999	D	0.715	prob.delet.	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.