TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21895	65908;65909;65910	chr2:178583120;178583119;178583118	chr2:179447847;179447846;179447845
N2AB	20254	60985;60986;60987	chr2:178583120;178583119;178583118	chr2:179447847;179447846;179447845
N2A	19327	58204;58205;58206	chr2:178583120;178583119;178583118	chr2:179447847;179447846;179447845
N2B	12830	38713;38714;38715	chr2:178583120;178583119;178583118	chr2:179447847;179447846;179447845
Novex-1	12955	39088;39089;39090	chr2:178583120;178583119;178583118	chr2:179447847;179447846;179447845
Novex-2	13022	39289;39290;39291	chr2:178583120;178583119;178583118	chr2:179447847;179447846;179447845
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: Ig-125
• Domain position: 30
• Structural Position: 46
• Q(SASA): 0.2143
• 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/L	None	None	0.031	D	0.461	0.188	0.445007932271	gnomAD-4.0.0	1.59553E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.865E-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
V/A	0.4631	ambiguous	0.41	ambiguous	-1.344	Destabilizing	0.296	N	0.677	prob.neutral	D	0.548315324	None	None	N
V/C	0.8609	likely_pathogenic	0.8306	pathogenic	-0.7	Destabilizing	0.991	D	0.724	prob.delet.	None	None	None	None	N
V/D	0.9616	likely_pathogenic	0.9479	pathogenic	-1.162	Destabilizing	0.879	D	0.867	deleterious	D	0.615026942	None	None	N
V/E	0.9066	likely_pathogenic	0.8862	pathogenic	-1.171	Destabilizing	0.906	D	0.848	deleterious	None	None	None	None	N
V/F	0.412	ambiguous	0.3525	ambiguous	-1.141	Destabilizing	0.782	D	0.771	deleterious	D	0.546720532	None	None	N
V/G	0.7317	likely_pathogenic	0.6745	pathogenic	-1.647	Destabilizing	0.879	D	0.859	deleterious	D	0.615026942	None	None	N
V/H	0.9529	likely_pathogenic	0.9351	pathogenic	-1.261	Destabilizing	0.991	D	0.837	deleterious	None	None	None	None	N
V/I	0.0771	likely_benign	0.0743	benign	-0.611	Destabilizing	0.001	N	0.211	neutral	N	0.490661135	None	None	N
V/K	0.9024	likely_pathogenic	0.879	pathogenic	-1.045	Destabilizing	0.906	D	0.847	deleterious	None	None	None	None	N
V/L	0.3426	ambiguous	0.281	benign	-0.611	Destabilizing	0.031	N	0.461	neutral	D	0.566035845	None	None	N
V/M	0.2842	likely_benign	0.2468	benign	-0.406	Destabilizing	0.826	D	0.67	neutral	None	None	None	None	N
V/N	0.8827	likely_pathogenic	0.8462	pathogenic	-0.732	Destabilizing	0.967	D	0.857	deleterious	None	None	None	None	N
V/P	0.8495	likely_pathogenic	0.85	pathogenic	-0.821	Destabilizing	0.967	D	0.839	deleterious	None	None	None	None	N
V/Q	0.8789	likely_pathogenic	0.8503	pathogenic	-0.893	Destabilizing	0.967	D	0.847	deleterious	None	None	None	None	N
V/R	0.8759	likely_pathogenic	0.8449	pathogenic	-0.571	Destabilizing	0.906	D	0.86	deleterious	None	None	None	None	N
V/S	0.7159	likely_pathogenic	0.6527	pathogenic	-1.194	Destabilizing	0.906	D	0.823	deleterious	None	None	None	None	N
V/T	0.5242	ambiguous	0.468	ambiguous	-1.088	Destabilizing	0.575	D	0.671	neutral	None	None	None	None	N
V/W	0.9622	likely_pathogenic	0.9528	pathogenic	-1.332	Destabilizing	0.991	D	0.825	deleterious	None	None	None	None	N
V/Y	0.8657	likely_pathogenic	0.8298	pathogenic	-1.036	Destabilizing	0.906	D	0.747	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.