TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21587	64984;64985;64986	chr2:178584882;178584881;178584880	chr2:179449609;179449608;179449607
N2AB	19946	60061;60062;60063	chr2:178584882;178584881;178584880	chr2:179449609;179449608;179449607
N2A	19019	57280;57281;57282	chr2:178584882;178584881;178584880	chr2:179449609;179449608;179449607
N2B	12522	37789;37790;37791	chr2:178584882;178584881;178584880	chr2:179449609;179449608;179449607
Novex-1	12647	38164;38165;38166	chr2:178584882;178584881;178584880	chr2:179449609;179449608;179449607
Novex-2	12714	38365;38366;38367	chr2:178584882;178584881;178584880	chr2:179449609;179449608;179449607
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-44
• Domain position: 29
• Structural Position: 30
• Q(SASA): 0.3443
• Predicted PPI site: I

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
D/G	None	None	0.928	N	0.693	0.523	0.51230852224	gnomAD-4.0.0	1.59218E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85982E-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
D/A	0.9094	likely_pathogenic	0.8902	pathogenic	-0.147	Destabilizing	0.957	D	0.701	prob.neutral	N	0.493551644	None	None	I
D/C	0.9912	likely_pathogenic	0.9875	pathogenic	0.238	Stabilizing	0.999	D	0.732	prob.delet.	None	None	None	None	I
D/E	0.8566	likely_pathogenic	0.8113	pathogenic	-0.577	Destabilizing	0.092	N	0.235	neutral	N	0.491221013	None	None	I
D/F	0.9908	likely_pathogenic	0.987	pathogenic	-0.436	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	I
D/G	0.8519	likely_pathogenic	0.8345	pathogenic	-0.386	Destabilizing	0.928	D	0.693	prob.neutral	N	0.517949776	None	None	I
D/H	0.9616	likely_pathogenic	0.9523	pathogenic	-0.808	Destabilizing	0.997	D	0.725	prob.delet.	N	0.510441358	None	None	I
D/I	0.9804	likely_pathogenic	0.9708	pathogenic	0.438	Stabilizing	0.992	D	0.768	deleterious	None	None	None	None	I
D/K	0.9716	likely_pathogenic	0.9663	pathogenic	0.157	Stabilizing	0.968	D	0.665	neutral	None	None	None	None	I
D/L	0.9726	likely_pathogenic	0.9615	pathogenic	0.438	Stabilizing	0.983	D	0.757	deleterious	None	None	None	None	I
D/M	0.9854	likely_pathogenic	0.9796	pathogenic	0.856	Stabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	I
D/N	0.4044	ambiguous	0.3109	benign	-0.064	Destabilizing	0.978	D	0.721	prob.delet.	N	0.468623761	None	None	I
D/P	0.9858	likely_pathogenic	0.9819	pathogenic	0.268	Stabilizing	0.992	D	0.756	deleterious	None	None	None	None	I
D/Q	0.9666	likely_pathogenic	0.9612	pathogenic	-0.01	Destabilizing	0.968	D	0.758	deleterious	None	None	None	None	I
D/R	0.9785	likely_pathogenic	0.977	pathogenic	0.031	Stabilizing	0.983	D	0.759	deleterious	None	None	None	None	I
D/S	0.7386	likely_pathogenic	0.6947	pathogenic	-0.186	Destabilizing	0.895	D	0.691	prob.neutral	None	None	None	None	I
D/T	0.8058	likely_pathogenic	0.7664	pathogenic	0.001	Stabilizing	0.983	D	0.739	prob.delet.	None	None	None	None	I
D/V	0.9451	likely_pathogenic	0.923	pathogenic	0.268	Stabilizing	0.978	D	0.762	deleterious	N	0.511909389	None	None	I
D/W	0.9976	likely_pathogenic	0.9972	pathogenic	-0.47	Destabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	I
D/Y	0.9254	likely_pathogenic	0.9091	pathogenic	-0.241	Destabilizing	0.999	D	0.744	deleterious	D	0.536054031	None	None	I

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.