TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20547	61864;61865;61866	chr2:178590086;178590085;178590084	chr2:179454813;179454812;179454811
N2AB	18906	56941;56942;56943	chr2:178590086;178590085;178590084	chr2:179454813;179454812;179454811
N2A	17979	54160;54161;54162	chr2:178590086;178590085;178590084	chr2:179454813;179454812;179454811
N2B	11482	34669;34670;34671	chr2:178590086;178590085;178590084	chr2:179454813;179454812;179454811
Novex-1	11607	35044;35045;35046	chr2:178590086;178590085;178590084	chr2:179454813;179454812;179454811
Novex-2	11674	35245;35246;35247	chr2:178590086;178590085;178590084	chr2:179454813;179454812;179454811
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-121
• Domain position: 69
• Structural Position: 154
• Q(SASA): 0.167
• 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
Y/S	None	None	1.0	D	0.886	0.805	0.871684563124	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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
Y/A	0.9994	likely_pathogenic	0.9993	pathogenic	-2.085	Highly Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
Y/C	0.9916	likely_pathogenic	0.992	pathogenic	-1.462	Destabilizing	1.0	D	0.861	deleterious	D	0.646458456	None	None	N
Y/D	0.9994	likely_pathogenic	0.9993	pathogenic	-2.49	Highly Destabilizing	1.0	D	0.889	deleterious	D	0.646458456	None	None	N
Y/E	0.9998	likely_pathogenic	0.9997	pathogenic	-2.239	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
Y/F	0.4676	ambiguous	0.4523	ambiguous	-0.592	Destabilizing	0.999	D	0.693	prob.neutral	D	0.581321989	None	None	N
Y/G	0.9978	likely_pathogenic	0.9977	pathogenic	-2.541	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
Y/H	0.9951	likely_pathogenic	0.9953	pathogenic	-1.789	Destabilizing	1.0	D	0.794	deleterious	D	0.646256652	None	None	N
Y/I	0.9779	likely_pathogenic	0.9759	pathogenic	-0.585	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Y/K	0.9998	likely_pathogenic	0.9997	pathogenic	-1.702	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
Y/L	0.955	likely_pathogenic	0.9547	pathogenic	-0.585	Destabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
Y/M	0.9927	likely_pathogenic	0.9924	pathogenic	-0.657	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
Y/N	0.9957	likely_pathogenic	0.9958	pathogenic	-2.601	Highly Destabilizing	1.0	D	0.883	deleterious	D	0.646458456	None	None	N
Y/P	0.9997	likely_pathogenic	0.9997	pathogenic	-1.099	Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
Y/Q	0.9998	likely_pathogenic	0.9998	pathogenic	-2.129	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
Y/R	0.9991	likely_pathogenic	0.9991	pathogenic	-2.015	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
Y/S	0.9987	likely_pathogenic	0.9986	pathogenic	-2.973	Highly Destabilizing	1.0	D	0.886	deleterious	D	0.646458456	None	None	N
Y/T	0.9993	likely_pathogenic	0.9992	pathogenic	-2.572	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/V	0.9725	likely_pathogenic	0.9706	pathogenic	-1.099	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
Y/W	0.9345	likely_pathogenic	0.9267	pathogenic	0.045	Stabilizing	1.0	D	0.787	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.