TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17010	51253;51254;51255	chr2:178611101;178611100;178611099	chr2:179475828;179475827;179475826
N2AB	15369	46330;46331;46332	chr2:178611101;178611100;178611099	chr2:179475828;179475827;179475826
N2A	14442	43549;43550;43551	chr2:178611101;178611100;178611099	chr2:179475828;179475827;179475826
N2B	7945	24058;24059;24060	chr2:178611101;178611100;178611099	chr2:179475828;179475827;179475826
Novex-1	8070	24433;24434;24435	chr2:178611101;178611100;178611099	chr2:179475828;179475827;179475826
Novex-2	8137	24634;24635;24636	chr2:178611101;178611100;178611099	chr2:179475828;179475827;179475826
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-111
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.101
• 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
A/V	rs1164633775	0.423	0.001	N	0.457	0.132	0.187945064343	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
A/V	rs1164633775	0.423	0.001	N	0.457	0.132	0.187945064343	gnomAD-4.0.0	1.59323E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43328E-05	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	0.4042	ambiguous	0.3736	ambiguous	-1.191	Destabilizing	0.005	N	0.521	neutral	None	None	None	None	N
A/D	0.9415	likely_pathogenic	0.9315	pathogenic	-2.647	Highly Destabilizing	0.69	D	0.79	deleterious	None	None	None	None	N
A/E	0.9085	likely_pathogenic	0.8889	pathogenic	-2.368	Highly Destabilizing	0.627	D	0.789	deleterious	N	0.497035598	None	None	N
A/F	0.656	likely_pathogenic	0.6113	pathogenic	-0.363	Destabilizing	0.69	D	0.798	deleterious	None	None	None	None	N
A/G	0.2525	likely_benign	0.254	benign	-1.425	Destabilizing	0.193	N	0.718	prob.delet.	N	0.453297002	None	None	N
A/H	0.8883	likely_pathogenic	0.8694	pathogenic	-2.225	Highly Destabilizing	0.981	D	0.755	deleterious	None	None	None	None	N
A/I	0.4	ambiguous	0.3443	ambiguous	0.632	Stabilizing	0.098	N	0.749	deleterious	None	None	None	None	N
A/K	0.9612	likely_pathogenic	0.9514	pathogenic	-1.016	Destabilizing	0.69	D	0.787	deleterious	None	None	None	None	N
A/L	0.3593	ambiguous	0.3149	benign	0.632	Stabilizing	0.002	N	0.597	neutral	None	None	None	None	N
A/M	0.4237	ambiguous	0.3711	ambiguous	0.093	Stabilizing	0.69	D	0.757	deleterious	None	None	None	None	N
A/N	0.7921	likely_pathogenic	0.7773	pathogenic	-1.598	Destabilizing	0.69	D	0.806	deleterious	None	None	None	None	N
A/P	0.9485	likely_pathogenic	0.9491	pathogenic	0.168	Stabilizing	0.773	D	0.793	deleterious	N	0.438370473	None	None	N
A/Q	0.856	likely_pathogenic	0.8298	pathogenic	-1.201	Destabilizing	0.818	D	0.782	deleterious	None	None	None	None	N
A/R	0.9261	likely_pathogenic	0.9051	pathogenic	-1.444	Destabilizing	0.69	D	0.798	deleterious	None	None	None	None	N
A/S	0.1411	likely_benign	0.1482	benign	-1.912	Destabilizing	0.015	N	0.507	neutral	N	0.436987728	None	None	N
A/T	0.1216	likely_benign	0.1142	benign	-1.494	Destabilizing	0.193	N	0.718	prob.delet.	N	0.437608206	None	None	N
A/V	0.187	likely_benign	0.1532	benign	0.168	Stabilizing	0.001	N	0.457	neutral	N	0.448284172	None	None	N
A/W	0.9455	likely_pathogenic	0.9334	pathogenic	-1.373	Destabilizing	0.981	D	0.779	deleterious	None	None	None	None	N
A/Y	0.82	likely_pathogenic	0.7937	pathogenic	-0.779	Destabilizing	0.818	D	0.775	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.