TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16734	50425;50426;50427	chr2:178612325;178612324;178612323	chr2:179477052;179477051;179477050
N2AB	15093	45502;45503;45504	chr2:178612325;178612324;178612323	chr2:179477052;179477051;179477050
N2A	14166	42721;42722;42723	chr2:178612325;178612324;178612323	chr2:179477052;179477051;179477050
N2B	7669	23230;23231;23232	chr2:178612325;178612324;178612323	chr2:179477052;179477051;179477050
Novex-1	7794	23605;23606;23607	chr2:178612325;178612324;178612323	chr2:179477052;179477051;179477050
Novex-2	7861	23806;23807;23808	chr2:178612325;178612324;178612323	chr2:179477052;179477051;179477050
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-9
• Domain position: 84
• Structural Position: 118
• Q(SASA): 0.081
• 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
S/G	rs1227059346	None	0.104	N	0.461	0.102	0.0762999501168	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
S/G	rs1227059346	None	0.104	N	0.461	0.102	0.0762999501168	gnomAD-4.0.0	6.5825E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47206E-05	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
S/A	0.3574	ambiguous	0.5584	ambiguous	-0.834	Destabilizing	0.98	D	0.68	prob.neutral	None	None	None	None	N
S/C	0.6727	likely_pathogenic	0.8132	pathogenic	-0.778	Destabilizing	1.0	D	0.73	prob.delet.	D	0.728166796	None	None	N
S/D	0.987	likely_pathogenic	0.9866	pathogenic	-1.546	Destabilizing	0.996	D	0.737	prob.delet.	None	None	None	None	N
S/E	0.9937	likely_pathogenic	0.9948	pathogenic	-1.434	Destabilizing	0.999	D	0.75	deleterious	None	None	None	None	N
S/F	0.9963	likely_pathogenic	0.9977	pathogenic	-0.659	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
S/G	0.1821	likely_benign	0.1751	benign	-1.161	Destabilizing	0.104	N	0.461	neutral	N	0.425422303	None	None	N
S/H	0.9896	likely_pathogenic	0.9916	pathogenic	-1.527	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
S/I	0.9937	likely_pathogenic	0.996	pathogenic	-0.032	Destabilizing	0.999	D	0.782	deleterious	D	0.690914888	None	None	N
S/K	0.9989	likely_pathogenic	0.999	pathogenic	-0.793	Destabilizing	0.996	D	0.749	deleterious	None	None	None	None	N
S/L	0.9746	likely_pathogenic	0.9844	pathogenic	-0.032	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
S/M	0.9796	likely_pathogenic	0.9861	pathogenic	0.01	Stabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
S/N	0.9449	likely_pathogenic	0.9507	pathogenic	-1.192	Destabilizing	0.994	D	0.727	prob.delet.	D	0.726088997	None	None	N
S/P	0.9947	likely_pathogenic	0.996	pathogenic	-0.266	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
S/Q	0.9919	likely_pathogenic	0.9945	pathogenic	-1.156	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
S/R	0.9977	likely_pathogenic	0.9985	pathogenic	-0.869	Destabilizing	1.0	D	0.759	deleterious	D	0.668088732	None	None	N
S/T	0.7348	likely_pathogenic	0.7509	pathogenic	-0.94	Destabilizing	0.994	D	0.7	prob.neutral	D	0.664942663	None	None	N
S/V	0.9841	likely_pathogenic	0.9909	pathogenic	-0.266	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
S/W	0.9964	likely_pathogenic	0.9974	pathogenic	-0.84	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
S/Y	0.9923	likely_pathogenic	0.9953	pathogenic	-0.479	Destabilizing	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.