TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5066	15421;15422;15423	chr2:178734728;178734727;178734726	chr2:179599455;179599454;179599453
N2AB	4749	14470;14471;14472	chr2:178734728;178734727;178734726	chr2:179599455;179599454;179599453
N2A	3822	11689;11690;11691	chr2:178734728;178734727;178734726	chr2:179599455;179599454;179599453
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: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-33
• Domain position: 86
• Structural Position: 171
• Q(SASA): 0.4313
• 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	rs756793304	-0.771	0.896	D	0.562	0.403	0.300110245524	gnomAD-2.1.1	1.79E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	3.91E-05	0
S/G	rs756793304	-0.771	0.896	D	0.562	0.403	0.300110245524	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	5.88E-05	0	0
S/G	rs756793304	-0.771	0.896	D	0.562	0.403	0.300110245524	gnomAD-4.0.0	4.96147E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.44727E-05	0	6.40841E-05

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	0.0948	likely_benign	0.0953	benign	-0.558	Destabilizing	0.702	D	0.549	neutral	None	None	None	None	N
S/C	0.1695	likely_benign	0.1731	benign	-0.251	Destabilizing	0.999	D	0.727	prob.delet.	D	0.733128236	None	None	N
S/D	0.5168	ambiguous	0.5166	ambiguous	-0.242	Destabilizing	0.851	D	0.531	neutral	None	None	None	None	N
S/E	0.6482	likely_pathogenic	0.6427	pathogenic	-0.336	Destabilizing	0.919	D	0.549	neutral	None	None	None	None	N
S/F	0.1791	likely_benign	0.1912	benign	-1.242	Destabilizing	0.988	D	0.798	deleterious	None	None	None	None	N
S/G	0.1311	likely_benign	0.1299	benign	-0.655	Destabilizing	0.896	D	0.562	neutral	D	0.622211869	None	None	N
S/H	0.4006	ambiguous	0.3793	ambiguous	-1.318	Destabilizing	0.997	D	0.733	prob.delet.	None	None	None	None	N
S/I	0.199	likely_benign	0.2033	benign	-0.423	Destabilizing	0.968	D	0.793	deleterious	D	0.560816177	None	None	N
S/K	0.7672	likely_pathogenic	0.7426	pathogenic	-0.468	Destabilizing	0.919	D	0.547	neutral	None	None	None	None	N
S/L	0.1072	likely_benign	0.1089	benign	-0.423	Destabilizing	0.851	D	0.741	deleterious	None	None	None	None	N
S/M	0.2093	likely_benign	0.2242	benign	0.106	Stabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
S/N	0.148	likely_benign	0.1511	benign	-0.212	Destabilizing	0.103	N	0.407	neutral	D	0.541392066	None	None	N
S/P	0.5899	likely_pathogenic	0.5342	ambiguous	-0.442	Destabilizing	0.988	D	0.744	deleterious	None	None	None	None	N
S/Q	0.5612	ambiguous	0.539	ambiguous	-0.569	Destabilizing	0.988	D	0.6	neutral	None	None	None	None	N
S/R	0.6865	likely_pathogenic	0.6336	pathogenic	-0.252	Destabilizing	0.984	D	0.735	prob.delet.	N	0.511377741	None	None	N
S/T	0.0717	likely_benign	0.0771	benign	-0.303	Destabilizing	0.046	N	0.265	neutral	N	0.494789785	None	None	N
S/V	0.1888	likely_benign	0.1939	benign	-0.442	Destabilizing	0.851	D	0.753	deleterious	None	None	None	None	N
S/W	0.4448	ambiguous	0.4313	ambiguous	-1.207	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
S/Y	0.231	likely_benign	0.2356	benign	-0.93	Destabilizing	0.996	D	0.799	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.