TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5831	17716;17717;17718	chr2:178731174;178731173;178731172	chr2:179595901;179595900;179595899
N2AB	5514	16765;16766;16767	chr2:178731174;178731173;178731172	chr2:179595901;179595900;179595899
N2A	4587	13984;13985;13986	chr2:178731174;178731173;178731172	chr2:179595901;179595900;179595899
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-42
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.3574
• 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
S/Y	rs760944340	-0.523	1.0	N	0.805	0.364	0.622579596728	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
S/Y	rs760944340	-0.523	1.0	N	0.805	0.364	0.622579596728	gnomAD-4.0.0	1.36868E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79925E-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
S/A	0.0897	likely_benign	0.1031	benign	-0.318	Destabilizing	0.997	D	0.414	neutral	N	0.510928393	None	None	N
S/C	0.1844	likely_benign	0.2413	benign	-0.317	Destabilizing	1.0	D	0.748	deleterious	N	0.485472297	None	None	N
S/D	0.3583	ambiguous	0.4198	ambiguous	0.232	Stabilizing	0.999	D	0.629	neutral	None	None	None	None	N
S/E	0.646	likely_pathogenic	0.7026	pathogenic	0.171	Stabilizing	0.999	D	0.617	neutral	None	None	None	None	N
S/F	0.3865	ambiguous	0.4473	ambiguous	-0.755	Destabilizing	1.0	D	0.812	deleterious	N	0.484711829	None	None	N
S/G	0.1138	likely_benign	0.125	benign	-0.483	Destabilizing	0.999	D	0.492	neutral	None	None	None	None	N
S/H	0.5605	ambiguous	0.5956	pathogenic	-0.957	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
S/I	0.3806	ambiguous	0.4544	ambiguous	-0.01	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
S/K	0.8602	likely_pathogenic	0.8967	pathogenic	-0.506	Destabilizing	0.999	D	0.614	neutral	None	None	None	None	N
S/L	0.1632	likely_benign	0.1898	benign	-0.01	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
S/M	0.3348	likely_benign	0.3811	ambiguous	0.073	Stabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
S/N	0.1671	likely_benign	0.1911	benign	-0.294	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
S/P	0.106	likely_benign	0.1196	benign	-0.08	Destabilizing	1.0	D	0.817	deleterious	N	0.488243534	None	None	N
S/Q	0.7113	likely_pathogenic	0.7455	pathogenic	-0.464	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
S/R	0.7954	likely_pathogenic	0.8412	pathogenic	-0.357	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
S/T	0.1015	likely_benign	0.1127	benign	-0.359	Destabilizing	0.999	D	0.467	neutral	N	0.453730331	None	None	N
S/V	0.3527	ambiguous	0.4119	ambiguous	-0.08	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
S/W	0.5586	ambiguous	0.5696	pathogenic	-0.786	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
S/Y	0.3499	ambiguous	0.4014	ambiguous	-0.493	Destabilizing	1.0	D	0.805	deleterious	N	0.484965318	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.