TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6190	18793;18794;18795	chr2:178729685;178729684;178729683	chr2:179594412;179594411;179594410
N2AB	5873	17842;17843;17844	chr2:178729685;178729684;178729683	chr2:179594412;179594411;179594410
N2A	4946	15061;15062;15063	chr2:178729685;178729684;178729683	chr2:179594412;179594411;179594410
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: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-45
• Domain position: 86
• Structural Position: 171
• Q(SASA): 0.3151
• 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/R	rs755474413	-0.299	0.949	N	0.726	0.467	0.531245695338	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
S/R	rs755474413	-0.299	0.949	N	0.726	0.467	0.531245695338	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07383E-04	0
S/R	rs755474413	-0.299	0.949	N	0.726	0.467	0.531245695338	gnomAD-4.0.0	3.09869E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.47672E-07	4.39203E-05	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	0.1016	benign	-0.319	Destabilizing	0.415	N	0.522	neutral	None	None	None	None	N
S/C	0.242	likely_benign	0.2644	benign	-0.294	Destabilizing	0.995	D	0.706	prob.neutral	D	0.558469106	None	None	N
S/D	0.3632	ambiguous	0.3417	ambiguous	0.17	Stabilizing	0.775	D	0.553	neutral	None	None	None	None	N
S/E	0.482	ambiguous	0.4447	ambiguous	0.095	Stabilizing	0.875	D	0.55	neutral	None	None	None	None	N
S/F	0.2161	likely_benign	0.2096	benign	-0.82	Destabilizing	0.987	D	0.79	deleterious	None	None	None	None	N
S/G	0.127	likely_benign	0.1194	benign	-0.464	Destabilizing	0.008	N	0.273	neutral	N	0.515068119	None	None	N
S/H	0.3372	likely_benign	0.3146	benign	-0.94	Destabilizing	0.996	D	0.701	prob.neutral	None	None	None	None	N
S/I	0.2205	likely_benign	0.2054	benign	-0.067	Destabilizing	0.901	D	0.788	deleterious	D	0.523475137	None	None	N
S/K	0.6474	likely_pathogenic	0.5858	pathogenic	-0.493	Destabilizing	0.775	D	0.542	neutral	None	None	None	None	N
S/L	0.1327	likely_benign	0.1265	benign	-0.067	Destabilizing	0.775	D	0.723	prob.delet.	None	None	None	None	N
S/M	0.2751	likely_benign	0.2624	benign	0.051	Stabilizing	0.996	D	0.7	prob.neutral	None	None	None	None	N
S/N	0.1407	likely_benign	0.1286	benign	-0.244	Destabilizing	0.722	D	0.567	neutral	N	0.496786053	None	None	N
S/P	0.3201	likely_benign	0.3556	ambiguous	-0.12	Destabilizing	0.987	D	0.728	prob.delet.	None	None	None	None	N
S/Q	0.474	ambiguous	0.4383	ambiguous	-0.446	Destabilizing	0.987	D	0.593	neutral	None	None	None	None	N
S/R	0.5021	ambiguous	0.4489	ambiguous	-0.309	Destabilizing	0.949	D	0.726	prob.delet.	N	0.487226947	None	None	N
S/T	0.0971	likely_benign	0.0943	benign	-0.318	Destabilizing	0.034	N	0.355	neutral	N	0.482578911	None	None	N
S/V	0.2313	likely_benign	0.2206	benign	-0.12	Destabilizing	0.923	D	0.737	prob.delet.	None	None	None	None	N
S/W	0.3759	ambiguous	0.375	ambiguous	-0.847	Destabilizing	0.996	D	0.765	deleterious	None	None	None	None	N
S/Y	0.2173	likely_benign	0.2107	benign	-0.556	Destabilizing	0.987	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.