TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31788	95587;95588;95589	chr2:178545874;178545873;178545872	chr2:179410601;179410600;179410599
N2AB	30147	90664;90665;90666	chr2:178545874;178545873;178545872	chr2:179410601;179410600;179410599
N2A	29220	87883;87884;87885	chr2:178545874;178545873;178545872	chr2:179410601;179410600;179410599
N2B	22723	68392;68393;68394	chr2:178545874;178545873;178545872	chr2:179410601;179410600;179410599
Novex-1	22848	68767;68768;68769	chr2:178545874;178545873;178545872	chr2:179410601;179410600;179410599
Novex-2	22915	68968;68969;68970	chr2:178545874;178545873;178545872	chr2:179410601;179410600;179410599
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: Fn3-119
• Domain position: 81
• Structural Position: 114
• Q(SASA): 0.7193
• 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
Y/C	rs397517761	None	1.0	N	0.756	0.42	0.425028116352	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
Y/H	rs1696861248	None	0.999	N	0.625	0.457	0.331365685468	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	1.47E-05	0	0
Y/H	rs1696861248	None	0.999	N	0.625	0.457	0.331365685468	gnomAD-4.0.0	1.31428E-05	None	None	None	None	I	None	2.41231E-05	0	None	0	0	None	0	0	1.47003E-05	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
Y/A	0.9279	likely_pathogenic	0.9384	pathogenic	-0.665	Destabilizing	0.996	D	0.643	neutral	None	None	None	None	I
Y/C	0.6137	likely_pathogenic	0.6373	pathogenic	0.06	Stabilizing	1.0	D	0.756	deleterious	N	0.468557628	None	None	I
Y/D	0.9211	likely_pathogenic	0.9198	pathogenic	1.0	Stabilizing	0.999	D	0.716	prob.delet.	N	0.494331204	None	None	I
Y/E	0.9781	likely_pathogenic	0.9752	pathogenic	0.984	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
Y/F	0.1123	likely_benign	0.1215	benign	-0.345	Destabilizing	0.217	N	0.293	neutral	N	0.45433411	None	None	I
Y/G	0.9348	likely_pathogenic	0.9354	pathogenic	-0.851	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	I
Y/H	0.6351	likely_pathogenic	0.5957	pathogenic	0.193	Stabilizing	0.999	D	0.625	neutral	N	0.465644339	None	None	I
Y/I	0.8173	likely_pathogenic	0.8315	pathogenic	-0.2	Destabilizing	0.998	D	0.639	neutral	None	None	None	None	I
Y/K	0.9815	likely_pathogenic	0.9777	pathogenic	0.228	Stabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
Y/L	0.8379	likely_pathogenic	0.8427	pathogenic	-0.2	Destabilizing	0.983	D	0.644	neutral	None	None	None	None	I
Y/M	0.8861	likely_pathogenic	0.8862	pathogenic	-0.07	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	I
Y/N	0.6888	likely_pathogenic	0.6917	pathogenic	0.048	Stabilizing	0.999	D	0.727	prob.delet.	N	0.473517924	None	None	I
Y/P	0.9939	likely_pathogenic	0.9924	pathogenic	-0.335	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	I
Y/Q	0.9584	likely_pathogenic	0.9497	pathogenic	0.096	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
Y/R	0.9594	likely_pathogenic	0.9496	pathogenic	0.47	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
Y/S	0.8534	likely_pathogenic	0.8717	pathogenic	-0.418	Destabilizing	0.999	D	0.694	prob.neutral	N	0.503568064	None	None	I
Y/T	0.9387	likely_pathogenic	0.9443	pathogenic	-0.341	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
Y/V	0.7571	likely_pathogenic	0.789	pathogenic	-0.335	Destabilizing	0.992	D	0.68	prob.neutral	None	None	None	None	I
Y/W	0.6385	likely_pathogenic	0.6165	pathogenic	-0.465	Destabilizing	1.0	D	0.622	neutral	None	None	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.