TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10114	30565;30566;30567	chr2:178702547;178702546;178702545	chr2:179567274;179567273;179567272
N2AB	9797	29614;29615;29616	chr2:178702547;178702546;178702545	chr2:179567274;179567273;179567272
N2A	8870	26833;26834;26835	chr2:178702547;178702546;178702545	chr2:179567274;179567273;179567272
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-86
• Domain position: 37
• Structural Position: 52
• Q(SASA): 0.8109
• 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
P/A	None	None	0.454	None	0.298	0.118	0.0846915920261	gnomAD-4.0.0	1.36827E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.7337E-04	0	0	1.65634E-05
P/S	None	None	0.454	None	0.286	0.135	0.0806252709748	gnomAD-4.0.0	4.1048E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39633E-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
P/A	0.2461	likely_benign	0.188	benign	-0.374	Destabilizing	0.454	N	0.298	neutral	None	None	None	None	N
P/C	0.9299	likely_pathogenic	0.9108	pathogenic	-0.795	Destabilizing	0.998	D	0.437	neutral	None	None	None	None	N
P/D	0.6989	likely_pathogenic	0.6569	pathogenic	-0.235	Destabilizing	0.016	N	0.157	neutral	None	None	None	None	N
P/E	0.5878	likely_pathogenic	0.5418	ambiguous	-0.342	Destabilizing	0.728	D	0.304	neutral	None	None	None	None	N
P/F	0.9235	likely_pathogenic	0.8883	pathogenic	-0.664	Destabilizing	0.974	D	0.449	neutral	None	None	None	None	N
P/G	0.7031	likely_pathogenic	0.6195	pathogenic	-0.45	Destabilizing	0.842	D	0.386	neutral	None	None	None	None	N
P/H	0.593	likely_pathogenic	0.5318	ambiguous	0.04	Stabilizing	0.998	D	0.391	neutral	None	None	None	None	N
P/I	0.8215	likely_pathogenic	0.7716	pathogenic	-0.315	Destabilizing	0.949	D	0.499	neutral	None	None	None	None	N
P/K	0.7126	likely_pathogenic	0.6626	pathogenic	-0.38	Destabilizing	0.016	N	0.207	neutral	None	None	None	None	N
P/L	0.4943	ambiguous	0.4403	ambiguous	-0.315	Destabilizing	0.669	D	0.453	neutral	None	None	None	None	N
P/M	0.7467	likely_pathogenic	0.682	pathogenic	-0.583	Destabilizing	0.998	D	0.389	neutral	None	None	None	None	N
P/N	0.6505	likely_pathogenic	0.577	pathogenic	-0.224	Destabilizing	0.842	D	0.443	neutral	None	None	None	None	N
P/Q	0.4578	ambiguous	0.3886	ambiguous	-0.413	Destabilizing	0.934	D	0.381	neutral	None	None	None	None	N
P/R	0.5765	likely_pathogenic	0.503	ambiguous	0.073	Stabilizing	0.669	D	0.454	neutral	None	None	None	None	N
P/S	0.3556	ambiguous	0.2706	benign	-0.558	Destabilizing	0.454	N	0.286	neutral	None	None	None	None	N
P/T	0.3164	likely_benign	0.2627	benign	-0.569	Destabilizing	0.022	N	0.128	neutral	None	None	None	None	N
P/V	0.7018	likely_pathogenic	0.6241	pathogenic	-0.306	Destabilizing	0.728	D	0.401	neutral	None	None	None	None	N
P/W	0.9614	likely_pathogenic	0.9439	pathogenic	-0.723	Destabilizing	0.998	D	0.527	neutral	None	None	None	None	N
P/Y	0.8915	likely_pathogenic	0.8498	pathogenic	-0.454	Destabilizing	0.991	D	0.449	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.