TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32193	96802;96803;96804	chr2:178543396;178543395;178543394	chr2:179408123;179408122;179408121
N2AB	30552	91879;91880;91881	chr2:178543396;178543395;178543394	chr2:179408123;179408122;179408121
N2A	29625	89098;89099;89100	chr2:178543396;178543395;178543394	chr2:179408123;179408122;179408121
N2B	23128	69607;69608;69609	chr2:178543396;178543395;178543394	chr2:179408123;179408122;179408121
Novex-1	23253	69982;69983;69984	chr2:178543396;178543395;178543394	chr2:179408123;179408122;179408121
Novex-2	23320	70183;70184;70185	chr2:178543396;178543395;178543394	chr2:179408123;179408122;179408121
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-122
• Domain position: 89
• Structural Position: 123
• Q(SASA): 0.2666
• 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
T/I	None	None	1.0	N	0.856	0.349	0.369682402691	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
T/A	0.4359	ambiguous	0.3409	ambiguous	-1.159	Destabilizing	0.986	D	0.692	prob.delet.	N	0.467121915	None	None	N
T/C	0.8402	likely_pathogenic	0.7724	pathogenic	-0.757	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
T/D	0.9567	likely_pathogenic	0.9482	pathogenic	-0.853	Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
T/E	0.9512	likely_pathogenic	0.9423	pathogenic	-0.716	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
T/F	0.8834	likely_pathogenic	0.8238	pathogenic	-0.835	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
T/G	0.7617	likely_pathogenic	0.7204	pathogenic	-1.545	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
T/H	0.9363	likely_pathogenic	0.9124	pathogenic	-1.641	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
T/I	0.5707	likely_pathogenic	0.4659	ambiguous	-0.166	Destabilizing	1.0	D	0.856	deleterious	N	0.464057268	None	None	N
T/K	0.9527	likely_pathogenic	0.9376	pathogenic	-0.646	Destabilizing	1.0	D	0.863	deleterious	N	0.506243714	None	None	N
T/L	0.2955	likely_benign	0.2387	benign	-0.166	Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	N
T/M	0.2309	likely_benign	0.1763	benign	-0.064	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
T/N	0.6553	likely_pathogenic	0.5991	pathogenic	-1.027	Destabilizing	0.999	D	0.818	deleterious	None	None	None	None	N
T/P	0.8414	likely_pathogenic	0.7976	pathogenic	-0.464	Destabilizing	0.999	D	0.829	deleterious	N	0.490865339	None	None	N
T/Q	0.911	likely_pathogenic	0.887	pathogenic	-0.953	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
T/R	0.9501	likely_pathogenic	0.9315	pathogenic	-0.682	Destabilizing	1.0	D	0.841	deleterious	N	0.494633919	None	None	N
T/S	0.4404	ambiguous	0.3778	ambiguous	-1.35	Destabilizing	0.986	D	0.727	deleterious	N	0.495119153	None	None	N
T/V	0.4647	ambiguous	0.3744	ambiguous	-0.464	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
T/W	0.9842	likely_pathogenic	0.9774	pathogenic	-0.837	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
T/Y	0.9346	likely_pathogenic	0.9099	pathogenic	-0.539	Destabilizing	1.0	D	0.86	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.