TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29968	90127;90128;90129	chr2:178552998;178552997;178552996	chr2:179417725;179417724;179417723
N2AB	28327	85204;85205;85206	chr2:178552998;178552997;178552996	chr2:179417725;179417724;179417723
N2A	27400	82423;82424;82425	chr2:178552998;178552997;178552996	chr2:179417725;179417724;179417723
N2B	20903	62932;62933;62934	chr2:178552998;178552997;178552996	chr2:179417725;179417724;179417723
Novex-1	21028	63307;63308;63309	chr2:178552998;178552997;178552996	chr2:179417725;179417724;179417723
Novex-2	21095	63508;63509;63510	chr2:178552998;178552997;178552996	chr2:179417725;179417724;179417723
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-106
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1143
• 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
Y/C	None	None	1.0	D	0.876	0.86	0.880978429174	gnomAD-4.0.0	1.59607E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43287E-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
Y/A	0.9959	likely_pathogenic	0.996	pathogenic	-3.512	Highly Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
Y/C	0.9288	likely_pathogenic	0.9177	pathogenic	-2.473	Highly Destabilizing	1.0	D	0.876	deleterious	D	0.669299878	None	None	N
Y/D	0.9949	likely_pathogenic	0.996	pathogenic	-3.822	Highly Destabilizing	1.0	D	0.908	deleterious	D	0.669501683	None	None	N
Y/E	0.999	likely_pathogenic	0.9991	pathogenic	-3.626	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
Y/F	0.2694	likely_benign	0.23	benign	-1.319	Destabilizing	0.999	D	0.637	neutral	D	0.588558377	None	None	N
Y/G	0.9903	likely_pathogenic	0.9908	pathogenic	-3.923	Highly Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
Y/H	0.9596	likely_pathogenic	0.9569	pathogenic	-2.47	Highly Destabilizing	1.0	D	0.798	deleterious	D	0.636857548	None	None	N
Y/I	0.9789	likely_pathogenic	0.9787	pathogenic	-2.133	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
Y/K	0.9982	likely_pathogenic	0.9983	pathogenic	-2.45	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
Y/L	0.957	likely_pathogenic	0.9617	pathogenic	-2.133	Highly Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
Y/M	0.9852	likely_pathogenic	0.9855	pathogenic	-2.067	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Y/N	0.9706	likely_pathogenic	0.9739	pathogenic	-3.203	Highly Destabilizing	1.0	D	0.891	deleterious	D	0.669299878	None	None	N
Y/P	0.9992	likely_pathogenic	0.9994	pathogenic	-2.609	Highly Destabilizing	1.0	D	0.935	deleterious	None	None	None	None	N
Y/Q	0.9978	likely_pathogenic	0.9978	pathogenic	-2.993	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
Y/R	0.9928	likely_pathogenic	0.9926	pathogenic	-2.085	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
Y/S	0.984	likely_pathogenic	0.9861	pathogenic	-3.595	Highly Destabilizing	1.0	D	0.899	deleterious	D	0.669299878	None	None	N
Y/T	0.9922	likely_pathogenic	0.9934	pathogenic	-3.276	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
Y/V	0.9581	likely_pathogenic	0.9611	pathogenic	-2.609	Highly Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
Y/W	0.8839	likely_pathogenic	0.8681	pathogenic	-0.589	Destabilizing	1.0	D	0.785	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.