TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7500	22723;22724;22725	chr2:178722289;178722288;178722287	chr2:179587016;179587015;179587014
N2AB	7183	21772;21773;21774	chr2:178722289;178722288;178722287	chr2:179587016;179587015;179587014
N2A	6256	18991;18992;18993	chr2:178722289;178722288;178722287	chr2:179587016;179587015;179587014
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-59
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.1488
• 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
A/S	rs1204148672	None	0.583	N	0.428	0.28	0.281381271821	gnomAD-4.0.0	6.88547E-07	None	None	None	None	I	None	0	2.2718E-05	None	0	0	None	0	0	0	0	0
A/V	rs1560689342	None	0.999	N	0.539	0.341	0.591496729656	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/V	rs1560689342	None	0.999	N	0.539	0.341	0.591496729656	gnomAD-4.0.0	6.57177E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47011E-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
A/C	0.7505	likely_pathogenic	0.7489	pathogenic	-0.733	Destabilizing	1.0	D	0.599	neutral	None	None	None	None	I
A/D	0.4032	ambiguous	0.4586	ambiguous	0.53	Stabilizing	1.0	D	0.637	neutral	None	None	None	None	I
A/E	0.5021	ambiguous	0.5532	ambiguous	0.429	Stabilizing	0.999	D	0.62	neutral	N	0.489353314	None	None	I
A/F	0.5518	ambiguous	0.5479	ambiguous	-0.728	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	I
A/G	0.2683	likely_benign	0.2701	benign	-0.453	Destabilizing	0.979	D	0.543	neutral	N	0.506865366	None	None	I
A/H	0.7231	likely_pathogenic	0.7385	pathogenic	-0.517	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
A/I	0.3665	ambiguous	0.3802	ambiguous	-0.186	Destabilizing	1.0	D	0.65	neutral	None	None	None	None	I
A/K	0.727	likely_pathogenic	0.7557	pathogenic	-0.304	Destabilizing	1.0	D	0.62	neutral	None	None	None	None	I
A/L	0.4136	ambiguous	0.4191	ambiguous	-0.186	Destabilizing	1.0	D	0.575	neutral	None	None	None	None	I
A/M	0.4252	ambiguous	0.4373	ambiguous	-0.356	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	I
A/N	0.4768	ambiguous	0.5199	ambiguous	-0.006	Destabilizing	0.996	D	0.626	neutral	None	None	None	None	I
A/P	0.9666	likely_pathogenic	0.9633	pathogenic	-0.197	Destabilizing	1.0	D	0.66	neutral	N	0.511891795	None	None	I
A/Q	0.5808	likely_pathogenic	0.6192	pathogenic	-0.149	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
A/R	0.6294	likely_pathogenic	0.6568	pathogenic	-0.114	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	I
A/S	0.1122	likely_benign	0.1188	benign	-0.422	Destabilizing	0.583	D	0.428	neutral	N	0.509086606	None	None	I
A/T	0.1142	likely_benign	0.1167	benign	-0.411	Destabilizing	0.81	D	0.401	neutral	N	0.520015676	None	None	I
A/V	0.1621	likely_benign	0.1742	benign	-0.197	Destabilizing	0.999	D	0.539	neutral	N	0.496560026	None	None	I
A/W	0.9349	likely_pathogenic	0.9367	pathogenic	-0.891	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
A/Y	0.7367	likely_pathogenic	0.7421	pathogenic	-0.5	Destabilizing	1.0	D	0.707	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.