TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22500	67723;67724;67725	chr2:178579699;178579698;178579697	chr2:179444426;179444425;179444424
N2AB	20859	62800;62801;62802	chr2:178579699;178579698;178579697	chr2:179444426;179444425;179444424
N2A	19932	60019;60020;60021	chr2:178579699;178579698;178579697	chr2:179444426;179444425;179444424
N2B	13435	40528;40529;40530	chr2:178579699;178579698;178579697	chr2:179444426;179444425;179444424
Novex-1	13560	40903;40904;40905	chr2:178579699;178579698;178579697	chr2:179444426;179444425;179444424
Novex-2	13627	41104;41105;41106	chr2:178579699;178579698;178579697	chr2:179444426;179444425;179444424
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-51
• Domain position: 50
• Structural Position: 68
• Q(SASA): 0.2021
• 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
V/G	rs760079543	None	0.998	N	0.725	0.491	0.859638543129	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	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
V/A	0.1802	likely_benign	0.2131	benign	-1.687	Destabilizing	0.954	D	0.515	neutral	N	0.485465093	None	None	N
V/C	0.6735	likely_pathogenic	0.6675	pathogenic	-1.024	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
V/D	0.5279	ambiguous	0.6412	pathogenic	-1.898	Destabilizing	0.998	D	0.763	deleterious	N	0.499374541	None	None	N
V/E	0.34	likely_benign	0.4408	ambiguous	-1.763	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
V/F	0.1862	likely_benign	0.2425	benign	-1.155	Destabilizing	0.989	D	0.678	prob.neutral	N	0.521153748	None	None	N
V/G	0.2421	likely_benign	0.2816	benign	-2.104	Highly Destabilizing	0.998	D	0.725	prob.delet.	N	0.488107141	None	None	N
V/H	0.5676	likely_pathogenic	0.6533	pathogenic	-1.551	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
V/I	0.0856	likely_benign	0.0918	benign	-0.576	Destabilizing	0.122	N	0.199	neutral	N	0.480461918	None	None	N
V/K	0.3062	likely_benign	0.384	ambiguous	-1.336	Destabilizing	0.999	D	0.72	prob.delet.	None	None	None	None	N
V/L	0.169	likely_benign	0.1951	benign	-0.576	Destabilizing	0.031	N	0.223	neutral	N	0.452640599	None	None	N
V/M	0.1509	likely_benign	0.1862	benign	-0.476	Destabilizing	0.991	D	0.586	neutral	None	None	None	None	N
V/N	0.397	ambiguous	0.4833	ambiguous	-1.461	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
V/P	0.7843	likely_pathogenic	0.8412	pathogenic	-0.917	Destabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	N
V/Q	0.323	likely_benign	0.3977	ambiguous	-1.457	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
V/R	0.2921	likely_benign	0.3696	ambiguous	-0.982	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
V/S	0.2907	likely_benign	0.3651	ambiguous	-2.008	Highly Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
V/T	0.2582	likely_benign	0.3044	benign	-1.741	Destabilizing	0.985	D	0.487	neutral	None	None	None	None	N
V/W	0.8027	likely_pathogenic	0.8669	pathogenic	-1.488	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
V/Y	0.5371	ambiguous	0.6148	pathogenic	-1.105	Destabilizing	0.999	D	0.693	prob.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.