TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18128	54607;54608;54609	chr2:178604305;178604304;178604303	chr2:179469032;179469031;179469030
N2AB	16487	49684;49685;49686	chr2:178604305;178604304;178604303	chr2:179469032;179469031;179469030
N2A	15560	46903;46904;46905	chr2:178604305;178604304;178604303	chr2:179469032;179469031;179469030
N2B	9063	27412;27413;27414	chr2:178604305;178604304;178604303	chr2:179469032;179469031;179469030
Novex-1	9188	27787;27788;27789	chr2:178604305;178604304;178604303	chr2:179469032;179469031;179469030
Novex-2	9255	27988;27989;27990	chr2:178604305;178604304;178604303	chr2:179469032;179469031;179469030
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-19
• Domain position: 64
• Structural Position: 93
• Q(SASA): 0.0805
• 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
I/S	rs765843072	-2.925	0.055	N	0.723	0.37	0.722937646298	gnomAD-2.1.1	1.26E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.55207E-04	None	0	0	0
I/S	rs765843072	-2.925	0.055	N	0.723	0.37	0.722937646298	gnomAD-4.0.0	1.00711E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.52202E-04	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
I/A	0.6414	likely_pathogenic	0.6892	pathogenic	-1.653	Destabilizing	0.007	N	0.617	neutral	None	None	None	None	N
I/C	0.7402	likely_pathogenic	0.7512	pathogenic	-0.752	Destabilizing	0.356	N	0.774	deleterious	None	None	None	None	N
I/D	0.9833	likely_pathogenic	0.9899	pathogenic	-2.261	Highly Destabilizing	0.356	N	0.8	deleterious	None	None	None	None	N
I/E	0.9611	likely_pathogenic	0.9769	pathogenic	-1.973	Destabilizing	0.136	N	0.769	deleterious	None	None	None	None	N
I/F	0.3656	ambiguous	0.4055	ambiguous	-1.051	Destabilizing	0.055	N	0.646	neutral	N	0.487062604	None	None	N
I/G	0.9359	likely_pathogenic	0.9569	pathogenic	-2.177	Highly Destabilizing	0.136	N	0.759	deleterious	None	None	None	None	N
I/H	0.9358	likely_pathogenic	0.9525	pathogenic	-2.071	Highly Destabilizing	0.864	D	0.815	deleterious	None	None	None	None	N
I/K	0.9292	likely_pathogenic	0.9604	pathogenic	-1.038	Destabilizing	0.136	N	0.763	deleterious	None	None	None	None	N
I/L	0.1522	likely_benign	0.1978	benign	-0.097	Destabilizing	None	N	0.183	neutral	N	0.443690255	None	None	N
I/M	0.2013	likely_benign	0.2329	benign	-0.209	Destabilizing	0.002	N	0.411	neutral	N	0.505477793	None	None	N
I/N	0.842	likely_pathogenic	0.8931	pathogenic	-1.676	Destabilizing	0.56	D	0.814	deleterious	N	0.516868223	None	None	N
I/P	0.9755	likely_pathogenic	0.9824	pathogenic	-0.605	Destabilizing	0.356	N	0.801	deleterious	None	None	None	None	N
I/Q	0.9186	likely_pathogenic	0.9474	pathogenic	-1.31	Destabilizing	0.356	N	0.814	deleterious	None	None	None	None	N
I/R	0.9046	likely_pathogenic	0.9381	pathogenic	-1.381	Destabilizing	0.356	N	0.808	deleterious	None	None	None	None	N
I/S	0.7884	likely_pathogenic	0.8356	pathogenic	-2.15	Highly Destabilizing	0.055	N	0.723	prob.delet.	N	0.505477793	None	None	N
I/T	0.6618	likely_pathogenic	0.7063	pathogenic	-1.703	Destabilizing	0.012	N	0.639	neutral	N	0.49191385	None	None	N
I/V	0.0709	likely_benign	0.071	benign	-0.605	Destabilizing	None	N	0.165	neutral	N	0.348761296	None	None	N
I/W	0.9653	likely_pathogenic	0.9741	pathogenic	-1.423	Destabilizing	0.864	D	0.811	deleterious	None	None	None	None	N
I/Y	0.8475	likely_pathogenic	0.8923	pathogenic	-1.081	Destabilizing	0.356	N	0.786	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.