TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3177	9754;9755;9756	chr2:178766555;178766554;178766553	chr2:179631282;179631281;179631280
N2AB	3177	9754;9755;9756	chr2:178766555;178766554;178766553	chr2:179631282;179631281;179631280
N2A	3177	9754;9755;9756	chr2:178766555;178766554;178766553	chr2:179631282;179631281;179631280
N2B	3131	9616;9617;9618	chr2:178766555;178766554;178766553	chr2:179631282;179631281;179631280
Novex-1	3131	9616;9617;9618	chr2:178766555;178766554;178766553	chr2:179631282;179631281;179631280
Novex-2	3131	9616;9617;9618	chr2:178766555;178766554;178766553	chr2:179631282;179631281;179631280
Novex-3	3177	9754;9755;9756	chr2:178766555;178766554;178766553	chr2:179631282;179631281;179631280

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-22
• Domain position: 31
• Structural Position: 46
• Q(SASA): 0.1302
• 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/D	None	None	0.801	N	0.801	0.586	0.688320708397	gnomAD-4.0.0	1.59067E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85662E-06	0	0
A/T	None	None	0.022	N	0.352	0.235	0.30212335484	gnomAD-4.0.0	2.40068E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62504E-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
A/C	0.7017	likely_pathogenic	0.7085	pathogenic	-0.809	Destabilizing	0.998	D	0.726	prob.delet.	None	None	None	None	N
A/D	0.9581	likely_pathogenic	0.9728	pathogenic	-2.34	Highly Destabilizing	0.801	D	0.801	deleterious	N	0.512923267	None	None	N
A/E	0.9365	likely_pathogenic	0.9593	pathogenic	-2.175	Highly Destabilizing	0.842	D	0.751	deleterious	None	None	None	None	N
A/F	0.9013	likely_pathogenic	0.9267	pathogenic	-1.031	Destabilizing	0.974	D	0.823	deleterious	None	None	None	None	N
A/G	0.3379	likely_benign	0.3973	ambiguous	-1.65	Destabilizing	0.005	N	0.297	neutral	N	0.38301733	None	None	N
A/H	0.9608	likely_pathogenic	0.9731	pathogenic	-1.888	Destabilizing	0.998	D	0.813	deleterious	None	None	None	None	N
A/I	0.7366	likely_pathogenic	0.7833	pathogenic	-0.217	Destabilizing	0.949	D	0.784	deleterious	None	None	None	None	N
A/K	0.975	likely_pathogenic	0.9861	pathogenic	-1.236	Destabilizing	0.842	D	0.754	deleterious	None	None	None	None	N
A/L	0.731	likely_pathogenic	0.7654	pathogenic	-0.217	Destabilizing	0.728	D	0.702	prob.neutral	None	None	None	None	N
A/M	0.7514	likely_pathogenic	0.8187	pathogenic	-0.2	Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
A/N	0.8932	likely_pathogenic	0.9217	pathogenic	-1.323	Destabilizing	0.949	D	0.81	deleterious	None	None	None	None	N
A/P	0.6873	likely_pathogenic	0.6494	pathogenic	-0.528	Destabilizing	0.012	N	0.51	neutral	N	0.486348146	None	None	N
A/Q	0.9254	likely_pathogenic	0.9505	pathogenic	-1.264	Destabilizing	0.974	D	0.786	deleterious	None	None	None	None	N
A/R	0.9436	likely_pathogenic	0.9623	pathogenic	-1.208	Destabilizing	0.949	D	0.791	deleterious	None	None	None	None	N
A/S	0.2057	likely_benign	0.2439	benign	-1.661	Destabilizing	0.454	N	0.634	neutral	N	0.506662276	None	None	N
A/T	0.2103	likely_benign	0.3016	benign	-1.391	Destabilizing	0.022	N	0.352	neutral	N	0.511093189	None	None	N
A/V	0.3981	ambiguous	0.4479	ambiguous	-0.528	Destabilizing	0.669	D	0.671	neutral	N	0.428408565	None	None	N
A/W	0.9866	likely_pathogenic	0.9912	pathogenic	-1.641	Destabilizing	0.998	D	0.815	deleterious	None	None	None	None	N
A/Y	0.9527	likely_pathogenic	0.9664	pathogenic	-1.111	Destabilizing	0.991	D	0.819	deleterious	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.