TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7490	22693;22694;22695	chr2:178722319;178722318;178722317	chr2:179587046;179587045;179587044
N2AB	7173	21742;21743;21744	chr2:178722319;178722318;178722317	chr2:179587046;179587045;179587044
N2A	6246	18961;18962;18963	chr2:178722319;178722318;178722317	chr2:179587046;179587045;179587044
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: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-59
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.1656
• 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/C	rs781659636	-0.898	0.997	N	0.683	0.384	0.799020525514	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
S/C	rs781659636	-0.898	0.997	N	0.683	0.384	0.799020525514	gnomAD-4.0.0	1.59472E-06	None	None	None	None	N	None	0	2.28938E-05	None	0	0	None	0	0	0	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	0.1125	likely_benign	0.1125	benign	-0.942	Destabilizing	0.267	N	0.421	neutral	N	0.494466465	None	None	N
S/C	0.175	likely_benign	0.1581	benign	-0.354	Destabilizing	0.997	D	0.683	prob.neutral	N	0.497304076	None	None	N
S/D	0.5556	ambiguous	0.5373	ambiguous	-0.512	Destabilizing	0.842	D	0.639	neutral	None	None	None	None	N
S/E	0.6445	likely_pathogenic	0.5983	pathogenic	-0.326	Destabilizing	0.842	D	0.623	neutral	None	None	None	None	N
S/F	0.1938	likely_benign	0.1808	benign	-0.967	Destabilizing	0.966	D	0.691	prob.neutral	N	0.496543607	None	None	N
S/G	0.1458	likely_benign	0.1496	benign	-1.315	Destabilizing	0.688	D	0.585	neutral	None	None	None	None	N
S/H	0.3199	likely_benign	0.3101	benign	-1.475	Destabilizing	0.998	D	0.69	prob.neutral	None	None	None	None	N
S/I	0.1359	likely_benign	0.1229	benign	0.013	Stabilizing	0.728	D	0.683	prob.neutral	None	None	None	None	N
S/K	0.7145	likely_pathogenic	0.6862	pathogenic	0.445	Stabilizing	0.067	N	0.313	neutral	None	None	None	None	N
S/L	0.1233	likely_benign	0.1175	benign	0.013	Stabilizing	0.525	D	0.67	neutral	None	None	None	None	N
S/M	0.2309	likely_benign	0.2178	benign	-0.028	Destabilizing	0.974	D	0.707	prob.neutral	None	None	None	None	N
S/N	0.1529	likely_benign	0.1646	benign	-0.129	Destabilizing	0.842	D	0.637	neutral	None	None	None	None	N
S/P	0.9662	likely_pathogenic	0.9649	pathogenic	-0.274	Destabilizing	0.966	D	0.719	prob.delet.	D	0.538120941	None	None	N
S/Q	0.5069	ambiguous	0.4781	ambiguous	0.036	Stabilizing	0.949	D	0.686	prob.neutral	None	None	None	None	N
S/R	0.5347	ambiguous	0.5107	ambiguous	0.046	Stabilizing	0.728	D	0.705	prob.neutral	None	None	None	None	N
S/T	0.0795	likely_benign	0.0756	benign	-0.006	Destabilizing	0.022	N	0.257	neutral	N	0.406231597	None	None	N
S/V	0.176	likely_benign	0.1648	benign	-0.274	Destabilizing	0.067	N	0.541	neutral	None	None	None	None	N
S/W	0.425	ambiguous	0.3957	ambiguous	-1.02	Destabilizing	0.998	D	0.733	prob.delet.	None	None	None	None	N
S/Y	0.2055	likely_benign	0.1971	benign	-0.607	Destabilizing	0.989	D	0.689	prob.neutral	N	0.493910261	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.