TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5832	17719;17720;17721	chr2:178731171;178731170;178731169	chr2:179595898;179595897;179595896
N2AB	5515	16768;16769;16770	chr2:178731171;178731170;178731169	chr2:179595898;179595897;179595896
N2A	4588	13987;13988;13989	chr2:178731171;178731170;178731169	chr2:179595898;179595897;179595896
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: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-42
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.2758
• 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/T	rs1222549953	-1.001	0.103	N	0.255	0.223	0.591820399129	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	1.11383E-04	None	0	None	0	0	1.65837E-04
I/T	rs1222549953	-1.001	0.103	N	0.255	0.223	0.591820399129	gnomAD-4.0.0	2.73726E-06	None	None	None	None	N	None	0	0	None	0	5.03931E-05	None	0	0	1.7992E-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
I/A	0.2683	likely_benign	0.3186	benign	-1.468	Destabilizing	0.702	D	0.473	neutral	None	None	None	None	N
I/C	0.7756	likely_pathogenic	0.8442	pathogenic	-0.927	Destabilizing	0.999	D	0.492	neutral	None	None	None	None	N
I/D	0.8413	likely_pathogenic	0.9103	pathogenic	-0.745	Destabilizing	0.988	D	0.594	neutral	None	None	None	None	N
I/E	0.6462	likely_pathogenic	0.7328	pathogenic	-0.758	Destabilizing	0.988	D	0.59	neutral	None	None	None	None	N
I/F	0.2113	likely_benign	0.2808	benign	-1.052	Destabilizing	0.988	D	0.431	neutral	None	None	None	None	N
I/G	0.7367	likely_pathogenic	0.824	pathogenic	-1.777	Destabilizing	0.988	D	0.547	neutral	None	None	None	None	N
I/H	0.7059	likely_pathogenic	0.7866	pathogenic	-1.025	Destabilizing	0.999	D	0.627	neutral	None	None	None	None	N
I/K	0.4469	ambiguous	0.554	ambiguous	-0.962	Destabilizing	0.984	D	0.592	neutral	N	0.505931658	None	None	N
I/L	0.1296	likely_benign	0.1541	benign	-0.706	Destabilizing	0.437	N	0.324	neutral	N	0.465525043	None	None	N
I/M	0.083	likely_benign	0.0972	benign	-0.559	Destabilizing	0.984	D	0.429	neutral	N	0.470298932	None	None	N
I/N	0.5086	ambiguous	0.6414	pathogenic	-0.729	Destabilizing	0.988	D	0.617	neutral	None	None	None	None	N
I/P	0.9032	likely_pathogenic	0.9451	pathogenic	-0.927	Destabilizing	0.996	D	0.617	neutral	None	None	None	None	N
I/Q	0.5488	ambiguous	0.62	pathogenic	-0.908	Destabilizing	0.996	D	0.631	neutral	None	None	None	None	N
I/R	0.3572	ambiguous	0.4559	ambiguous	-0.406	Destabilizing	0.984	D	0.619	neutral	D	0.525133494	None	None	N
I/S	0.3851	ambiguous	0.4739	ambiguous	-1.354	Destabilizing	0.851	D	0.507	neutral	None	None	None	None	N
I/T	0.1247	likely_benign	0.1614	benign	-1.247	Destabilizing	0.103	N	0.255	neutral	N	0.455310837	None	None	N
I/V	0.0717	likely_benign	0.0759	benign	-0.927	Destabilizing	0.011	N	0.103	neutral	N	0.415805512	None	None	N
I/W	0.8016	likely_pathogenic	0.8622	pathogenic	-1.1	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
I/Y	0.6736	likely_pathogenic	0.7576	pathogenic	-0.874	Destabilizing	0.996	D	0.499	neutral	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.