TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21733	65422;65423;65424	chr2:178584354;178584353;178584352	chr2:179449081;179449080;179449079
N2AB	20092	60499;60500;60501	chr2:178584354;178584353;178584352	chr2:179449081;179449080;179449079
N2A	19165	57718;57719;57720	chr2:178584354;178584353;178584352	chr2:179449081;179449080;179449079
N2B	12668	38227;38228;38229	chr2:178584354;178584353;178584352	chr2:179449081;179449080;179449079
Novex-1	12793	38602;38603;38604	chr2:178584354;178584353;178584352	chr2:179449081;179449080;179449079
Novex-2	12860	38803;38804;38805	chr2:178584354;178584353;178584352	chr2:179449081;179449080;179449079
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-45
• Domain position: 75
• Structural Position: 107
• Q(SASA): 0.1357
• 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
R/G	None	None	0.822	D	0.582	0.513	0.614227455099	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
R/I	None	None	0.971	D	0.726	0.479	0.774314364548	gnomAD-4.0.0	2.73851E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69984E-06	0	1.65772E-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
R/A	0.9905	likely_pathogenic	0.9921	pathogenic	-2.105	Highly Destabilizing	0.754	D	0.55	neutral	None	None	None	None	N
R/C	0.6806	likely_pathogenic	0.7502	pathogenic	-1.851	Destabilizing	0.998	D	0.722	prob.delet.	None	None	None	None	N
R/D	0.999	likely_pathogenic	0.9989	pathogenic	-1.239	Destabilizing	0.956	D	0.632	neutral	None	None	None	None	N
R/E	0.9876	likely_pathogenic	0.9889	pathogenic	-1.008	Destabilizing	0.754	D	0.533	neutral	None	None	None	None	N
R/F	0.993	likely_pathogenic	0.9953	pathogenic	-1.19	Destabilizing	0.993	D	0.741	deleterious	None	None	None	None	N
R/G	0.9876	likely_pathogenic	0.9891	pathogenic	-2.44	Highly Destabilizing	0.822	D	0.582	neutral	D	0.544932029	None	None	N
R/H	0.5738	likely_pathogenic	0.5907	pathogenic	-2.131	Highly Destabilizing	0.978	D	0.593	neutral	None	None	None	None	N
R/I	0.9724	likely_pathogenic	0.9816	pathogenic	-1.113	Destabilizing	0.971	D	0.726	prob.delet.	D	0.526827774	None	None	N
R/K	0.582	likely_pathogenic	0.6257	pathogenic	-1.151	Destabilizing	0.014	N	0.303	neutral	N	0.480589177	None	None	N
R/L	0.9517	likely_pathogenic	0.96	pathogenic	-1.113	Destabilizing	0.86	D	0.582	neutral	None	None	None	None	N
R/M	0.9784	likely_pathogenic	0.9866	pathogenic	-1.615	Destabilizing	0.998	D	0.629	neutral	None	None	None	None	N
R/N	0.9943	likely_pathogenic	0.9948	pathogenic	-1.412	Destabilizing	0.956	D	0.528	neutral	None	None	None	None	N
R/P	0.9994	likely_pathogenic	0.9993	pathogenic	-1.436	Destabilizing	0.978	D	0.663	neutral	None	None	None	None	N
R/Q	0.6019	likely_pathogenic	0.6372	pathogenic	-1.196	Destabilizing	0.915	D	0.53	neutral	None	None	None	None	N
R/S	0.993	likely_pathogenic	0.9941	pathogenic	-2.225	Highly Destabilizing	0.698	D	0.541	neutral	N	0.509707343	None	None	N
R/T	0.9893	likely_pathogenic	0.992	pathogenic	-1.785	Destabilizing	0.942	D	0.565	neutral	N	0.497959417	None	None	N
R/V	0.976	likely_pathogenic	0.9827	pathogenic	-1.436	Destabilizing	0.956	D	0.695	prob.neutral	None	None	None	None	N
R/W	0.9037	likely_pathogenic	0.9248	pathogenic	-0.744	Destabilizing	0.998	D	0.675	neutral	None	None	None	None	N
R/Y	0.9709	likely_pathogenic	0.9808	pathogenic	-0.654	Destabilizing	0.993	D	0.699	prob.neutral	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.