TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23807	71644;71645;71646	chr2:178574713;178574712;178574711	chr2:179439440;179439439;179439438
N2AB	22166	66721;66722;66723	chr2:178574713;178574712;178574711	chr2:179439440;179439439;179439438
N2A	21239	63940;63941;63942	chr2:178574713;178574712;178574711	chr2:179439440;179439439;179439438
N2B	14742	44449;44450;44451	chr2:178574713;178574712;178574711	chr2:179439440;179439439;179439438
Novex-1	14867	44824;44825;44826	chr2:178574713;178574712;178574711	chr2:179439440;179439439;179439438
Novex-2	14934	45025;45026;45027	chr2:178574713;178574712;178574711	chr2:179439440;179439439;179439438
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: Fn3-60
• Domain position: 82
• Structural Position: 114
• Q(SASA): 0.6835
• 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/H	rs1709451594	None	1.0	N	0.711	0.515	0.336892272479	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-05	0	None	0	0	None	0	0	0	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	0.9772	likely_pathogenic	0.9721	pathogenic	-0.597	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	I
Y/C	0.6769	likely_pathogenic	0.6723	pathogenic	0.036	Stabilizing	1.0	D	0.79	deleterious	N	0.475963914	None	None	I
Y/D	0.9643	likely_pathogenic	0.9614	pathogenic	0.669	Stabilizing	1.0	D	0.761	deleterious	N	0.484949908	None	None	I
Y/E	0.9918	likely_pathogenic	0.9908	pathogenic	0.659	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
Y/F	0.1483	likely_benign	0.1498	benign	-0.266	Destabilizing	0.999	D	0.517	neutral	N	0.445445268	None	None	I
Y/G	0.955	likely_pathogenic	0.9507	pathogenic	-0.782	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	I
Y/H	0.7558	likely_pathogenic	0.7455	pathogenic	0.242	Stabilizing	1.0	D	0.711	prob.delet.	N	0.501855911	None	None	I
Y/I	0.9319	likely_pathogenic	0.9327	pathogenic	-0.126	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
Y/K	0.9847	likely_pathogenic	0.9838	pathogenic	0.12	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
Y/L	0.865	likely_pathogenic	0.8647	pathogenic	-0.126	Destabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	I
Y/M	0.9415	likely_pathogenic	0.9415	pathogenic	-0.156	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
Y/N	0.8538	likely_pathogenic	0.8351	pathogenic	-0.141	Destabilizing	1.0	D	0.768	deleterious	N	0.514091702	None	None	I
Y/P	0.9962	likely_pathogenic	0.996	pathogenic	-0.265	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	I
Y/Q	0.9774	likely_pathogenic	0.9728	pathogenic	-0.06	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	I
Y/R	0.9598	likely_pathogenic	0.9585	pathogenic	0.307	Stabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
Y/S	0.9222	likely_pathogenic	0.9066	pathogenic	-0.497	Destabilizing	1.0	D	0.751	deleterious	N	0.511379471	None	None	I
Y/T	0.9776	likely_pathogenic	0.9747	pathogenic	-0.415	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
Y/V	0.8967	likely_pathogenic	0.8954	pathogenic	-0.265	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
Y/W	0.6557	likely_pathogenic	0.6602	pathogenic	-0.404	Destabilizing	1.0	D	0.699	prob.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.