TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31931	96016;96017;96018	chr2:178544438;178544437;178544436	chr2:179409165;179409164;179409163
N2AB	30290	91093;91094;91095	chr2:178544438;178544437;178544436	chr2:179409165;179409164;179409163
N2A	29363	88312;88313;88314	chr2:178544438;178544437;178544436	chr2:179409165;179409164;179409163
N2B	22866	68821;68822;68823	chr2:178544438;178544437;178544436	chr2:179409165;179409164;179409163
Novex-1	22991	69196;69197;69198	chr2:178544438;178544437;178544436	chr2:179409165;179409164;179409163
Novex-2	23058	69397;69398;69399	chr2:178544438;178544437;178544436	chr2:179409165;179409164;179409163
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-121
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.4278
• 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/N	None	None	0.982	N	0.619	0.304	0.425148423609	gnomAD-4.0.0	2.73702E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69863E-06	0	1.65651E-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
T/A	0.0907	likely_benign	0.088	benign	-1.01	Destabilizing	0.76	D	0.387	neutral	N	0.464321817	None	None	I
T/C	0.3668	ambiguous	0.3757	ambiguous	-0.632	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	I
T/D	0.4699	ambiguous	0.3988	ambiguous	-0.583	Destabilizing	0.986	D	0.755	deleterious	None	None	None	None	I
T/E	0.3768	ambiguous	0.3111	benign	-0.527	Destabilizing	0.986	D	0.76	deleterious	None	None	None	None	I
T/F	0.3388	likely_benign	0.3123	benign	-0.939	Destabilizing	0.998	D	0.796	deleterious	None	None	None	None	I
T/G	0.1543	likely_benign	0.1608	benign	-1.331	Destabilizing	0.91	D	0.642	neutral	None	None	None	None	I
T/H	0.3052	likely_benign	0.2723	benign	-1.603	Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	I
T/I	0.2316	likely_benign	0.2211	benign	-0.223	Destabilizing	0.991	D	0.777	deleterious	N	0.472840496	None	None	I
T/K	0.2661	likely_benign	0.215	benign	-0.87	Destabilizing	0.986	D	0.761	deleterious	None	None	None	None	I
T/L	0.1152	likely_benign	0.1078	benign	-0.223	Destabilizing	0.953	D	0.641	neutral	None	None	None	None	I
T/M	0.0931	likely_benign	0.0876	benign	0.042	Stabilizing	0.999	D	0.743	deleterious	None	None	None	None	I
T/N	0.1123	likely_benign	0.1051	benign	-0.993	Destabilizing	0.982	D	0.619	neutral	N	0.492084421	None	None	I
T/P	0.2308	likely_benign	0.1894	benign	-0.452	Destabilizing	0.991	D	0.778	deleterious	N	0.479841935	None	None	I
T/Q	0.2374	likely_benign	0.2059	benign	-1.038	Destabilizing	0.993	D	0.783	deleterious	None	None	None	None	I
T/R	0.2585	likely_benign	0.1935	benign	-0.744	Destabilizing	0.986	D	0.781	deleterious	None	None	None	None	I
T/S	0.0948	likely_benign	0.0946	benign	-1.258	Destabilizing	0.17	N	0.216	neutral	N	0.452293882	None	None	I
T/V	0.1651	likely_benign	0.1656	benign	-0.452	Destabilizing	0.953	D	0.537	neutral	None	None	None	None	I
T/W	0.6965	likely_pathogenic	0.6494	pathogenic	-0.914	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	I
T/Y	0.3721	ambiguous	0.3398	benign	-0.666	Destabilizing	0.998	D	0.797	deleterious	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.