TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6207	18844;18845;18846	chr2:178729537;178729536;178729535	chr2:179594264;179594263;179594262
N2AB	5890	17893;17894;17895	chr2:178729537;178729536;178729535	chr2:179594264;179594263;179594262
N2A	4963	15112;15113;15114	chr2:178729537;178729536;178729535	chr2:179594264;179594263;179594262
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: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-46
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.3186
• 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
P/A	rs755803926	-0.766	0.039	N	0.405	0.215	0.112648838833	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
P/A	rs755803926	-0.766	0.039	N	0.405	0.215	0.112648838833	gnomAD-4.0.0	1.5931E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43345E-05	0
P/S	None	None	0.957	N	0.708	0.312	0.126345400529	gnomAD-4.0.0	3.18619E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72439E-06	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
P/A	0.076	likely_benign	0.0847	benign	-0.519	Destabilizing	0.039	N	0.405	neutral	N	0.502711555	None	None	N
P/C	0.606	likely_pathogenic	0.6787	pathogenic	-0.556	Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
P/D	0.2801	likely_benign	0.3024	benign	-0.496	Destabilizing	0.992	D	0.786	deleterious	None	None	None	None	N
P/E	0.2195	likely_benign	0.2502	benign	-0.602	Destabilizing	0.983	D	0.78	deleterious	None	None	None	None	N
P/F	0.5166	ambiguous	0.5992	pathogenic	-0.709	Destabilizing	0.998	D	0.787	deleterious	None	None	None	None	N
P/G	0.2811	likely_benign	0.3202	benign	-0.665	Destabilizing	0.895	D	0.702	prob.neutral	None	None	None	None	N
P/H	0.2059	likely_benign	0.2394	benign	-0.27	Destabilizing	0.999	D	0.738	prob.delet.	N	0.454793515	None	None	N
P/I	0.3946	ambiguous	0.4702	ambiguous	-0.279	Destabilizing	0.983	D	0.806	deleterious	None	None	None	None	N
P/K	0.3382	likely_benign	0.3723	ambiguous	-0.561	Destabilizing	0.983	D	0.787	deleterious	None	None	None	None	N
P/L	0.1472	likely_benign	0.1732	benign	-0.279	Destabilizing	0.957	D	0.769	deleterious	N	0.495342865	None	None	N
P/M	0.3199	likely_benign	0.375	ambiguous	-0.356	Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
P/N	0.2438	likely_benign	0.273	benign	-0.249	Destabilizing	0.992	D	0.806	deleterious	None	None	None	None	N
P/Q	0.1636	likely_benign	0.1919	benign	-0.493	Destabilizing	0.992	D	0.807	deleterious	None	None	None	None	N
P/R	0.2175	likely_benign	0.2502	benign	-0.031	Destabilizing	0.978	D	0.804	deleterious	N	0.511235037	None	None	N
P/S	0.1088	likely_benign	0.1229	benign	-0.571	Destabilizing	0.957	D	0.708	prob.delet.	N	0.425480135	None	None	N
P/T	0.1008	likely_benign	0.1218	benign	-0.581	Destabilizing	0.978	D	0.719	prob.delet.	N	0.495822868	None	None	N
P/V	0.2555	likely_benign	0.3039	benign	-0.324	Destabilizing	0.968	D	0.72	prob.delet.	None	None	None	None	N
P/W	0.6587	likely_pathogenic	0.7315	pathogenic	-0.811	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
P/Y	0.4448	ambiguous	0.5102	ambiguous	-0.517	Destabilizing	0.999	D	0.784	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.