TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26893	80902;80903;80904	chr2:178565455;178565454;178565453	chr2:179430182;179430181;179430180
N2AB	25252	75979;75980;75981	chr2:178565455;178565454;178565453	chr2:179430182;179430181;179430180
N2A	24325	73198;73199;73200	chr2:178565455;178565454;178565453	chr2:179430182;179430181;179430180
N2B	17828	53707;53708;53709	chr2:178565455;178565454;178565453	chr2:179430182;179430181;179430180
Novex-1	17953	54082;54083;54084	chr2:178565455;178565454;178565453	chr2:179430182;179430181;179430180
Novex-2	18020	54283;54284;54285	chr2:178565455;178565454;178565453	chr2:179430182;179430181;179430180
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-139
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.2213
• Predicted PPI site: N

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
A/G	rs1273776382	None	0.826	N	0.44	0.283	0.246215685461	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	0	4.77555E-04
A/G	rs1273776382	None	0.826	N	0.44	0.283	0.246215685461	gnomAD-4.0.0	2.56383E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.39404E-06	0	2.84706E-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
A/C	0.4802	ambiguous	0.5116	ambiguous	-0.791	Destabilizing	0.999	D	0.439	neutral	None	None	None	None	N
A/D	0.4694	ambiguous	0.4974	ambiguous	-0.825	Destabilizing	0.852	D	0.421	neutral	N	0.460429055	None	None	N
A/E	0.3351	likely_benign	0.3677	ambiguous	-0.969	Destabilizing	0.884	D	0.409	neutral	None	None	None	None	N
A/F	0.4234	ambiguous	0.4267	ambiguous	-1.06	Destabilizing	0.997	D	0.429	neutral	None	None	None	None	N
A/G	0.152	likely_benign	0.1637	benign	-0.663	Destabilizing	0.826	D	0.44	neutral	N	0.492611867	None	None	N
A/H	0.5377	ambiguous	0.568	pathogenic	-0.697	Destabilizing	0.991	D	0.423	neutral	None	None	None	None	N
A/I	0.26	likely_benign	0.2693	benign	-0.498	Destabilizing	0.991	D	0.419	neutral	None	None	None	None	N
A/K	0.4682	ambiguous	0.5156	ambiguous	-0.916	Destabilizing	0.884	D	0.418	neutral	None	None	None	None	N
A/L	0.2521	likely_benign	0.2638	benign	-0.498	Destabilizing	0.969	D	0.407	neutral	None	None	None	None	N
A/M	0.2536	likely_benign	0.2602	benign	-0.395	Destabilizing	0.999	D	0.413	neutral	None	None	None	None	N
A/N	0.3035	likely_benign	0.323	benign	-0.54	Destabilizing	0.079	N	0.259	neutral	None	None	None	None	N
A/P	0.4286	ambiguous	0.4571	ambiguous	-0.484	Destabilizing	0.988	D	0.409	neutral	N	0.504925141	None	None	N
A/Q	0.3774	ambiguous	0.4127	ambiguous	-0.859	Destabilizing	0.579	D	0.3	neutral	None	None	None	None	N
A/R	0.4545	ambiguous	0.4995	ambiguous	-0.384	Destabilizing	0.939	D	0.418	neutral	None	None	None	None	N
A/S	0.0998	likely_benign	0.103	benign	-0.753	Destabilizing	0.31	N	0.262	neutral	N	0.472236719	None	None	N
A/T	0.1103	likely_benign	0.1131	benign	-0.824	Destabilizing	0.852	D	0.435	neutral	N	0.454312989	None	None	N
A/V	0.1233	likely_benign	0.1271	benign	-0.484	Destabilizing	0.959	D	0.47	neutral	N	0.442777817	None	None	N
A/W	0.8118	likely_pathogenic	0.8239	pathogenic	-1.203	Destabilizing	0.999	D	0.524	neutral	None	None	None	None	N
A/Y	0.548	ambiguous	0.5709	pathogenic	-0.872	Destabilizing	0.997	D	0.429	neutral	None	None	None	None	N

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.