TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25716	77371;77372;77373	chr2:178568986;178568985;178568984	chr2:179433713;179433712;179433711
N2AB	24075	72448;72449;72450	chr2:178568986;178568985;178568984	chr2:179433713;179433712;179433711
N2A	23148	69667;69668;69669	chr2:178568986;178568985;178568984	chr2:179433713;179433712;179433711
N2B	16651	50176;50177;50178	chr2:178568986;178568985;178568984	chr2:179433713;179433712;179433711
Novex-1	16776	50551;50552;50553	chr2:178568986;178568985;178568984	chr2:179433713;179433712;179433711
Novex-2	16843	50752;50753;50754	chr2:178568986;178568985;178568984	chr2:179433713;179433712;179433711
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-75
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.1553
• 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/P	None	None	1.0	N	0.733	0.455	0.339316883193	gnomAD-4.0.0	6.84348E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99614E-07	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	0.105	likely_benign	0.0928	benign	-0.759	Destabilizing	0.988	D	0.519	neutral	N	0.494335293	None	None	N
S/C	0.1235	likely_benign	0.1073	benign	-0.79	Destabilizing	1.0	D	0.786	deleterious	N	0.475220353	None	None	N
S/D	0.6883	likely_pathogenic	0.6187	pathogenic	-1.035	Destabilizing	1.0	D	0.599	neutral	None	None	None	None	N
S/E	0.7185	likely_pathogenic	0.6471	pathogenic	-0.992	Destabilizing	1.0	D	0.605	neutral	None	None	None	None	N
S/F	0.217	likely_benign	0.1405	benign	-0.965	Destabilizing	1.0	D	0.805	deleterious	D	0.523850123	None	None	N
S/G	0.1722	likely_benign	0.161	benign	-1.026	Destabilizing	1.0	D	0.603	neutral	None	None	None	None	N
S/H	0.3818	ambiguous	0.3108	benign	-1.546	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
S/I	0.177	likely_benign	0.1416	benign	-0.146	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
S/K	0.7478	likely_pathogenic	0.6821	pathogenic	-0.691	Destabilizing	1.0	D	0.6	neutral	None	None	None	None	N
S/L	0.1076	likely_benign	0.0903	benign	-0.146	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
S/M	0.1912	likely_benign	0.1616	benign	0.05	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
S/N	0.2174	likely_benign	0.197	benign	-0.919	Destabilizing	0.998	D	0.612	neutral	None	None	None	None	N
S/P	0.9526	likely_pathogenic	0.9045	pathogenic	-0.317	Destabilizing	1.0	D	0.733	prob.delet.	N	0.493071118	None	None	N
S/Q	0.5736	likely_pathogenic	0.4985	ambiguous	-1.057	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
S/R	0.653	likely_pathogenic	0.5775	pathogenic	-0.645	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
S/T	0.0751	likely_benign	0.0719	benign	-0.798	Destabilizing	0.997	D	0.573	neutral	N	0.383530017	None	None	N
S/V	0.1925	likely_benign	0.1569	benign	-0.317	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
S/W	0.4255	ambiguous	0.299	benign	-1.008	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
S/Y	0.2436	likely_benign	0.1699	benign	-0.672	Destabilizing	1.0	D	0.815	deleterious	N	0.521156535	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.