TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25914	77965;77966;77967	chr2:178568392;178568391;178568390	chr2:179433119;179433118;179433117
N2AB	24273	73042;73043;73044	chr2:178568392;178568391;178568390	chr2:179433119;179433118;179433117
N2A	23346	70261;70262;70263	chr2:178568392;178568391;178568390	chr2:179433119;179433118;179433117
N2B	16849	50770;50771;50772	chr2:178568392;178568391;178568390	chr2:179433119;179433118;179433117
Novex-1	16974	51145;51146;51147	chr2:178568392;178568391;178568390	chr2:179433119;179433118;179433117
Novex-2	17041	51346;51347;51348	chr2:178568392;178568391;178568390	chr2:179433119;179433118;179433117
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-76
• Domain position: 25
• Structural Position: 26
• Q(SASA): 0.4204
• 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
P/R	rs774671830	-1.107	0.989	N	0.884	0.485	0.652424105921	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.65E-05	0	0
P/R	rs774671830	-1.107	0.989	N	0.884	0.485	0.652424105921	gnomAD-4.0.0	1.59268E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88445E-05	0	0	0	0
P/S	None	None	0.989	N	0.808	0.439	0.465038187318	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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
P/A	0.0788	likely_benign	0.0872	benign	-1.775	Destabilizing	0.928	D	0.66	neutral	N	0.504226999	None	None	N
P/C	0.5663	likely_pathogenic	0.6154	pathogenic	-1.16	Destabilizing	0.999	D	0.879	deleterious	None	None	None	None	N
P/D	0.7314	likely_pathogenic	0.7838	pathogenic	-1.89	Destabilizing	0.997	D	0.841	deleterious	None	None	None	None	N
P/E	0.3633	ambiguous	0.3946	ambiguous	-1.793	Destabilizing	0.992	D	0.822	deleterious	None	None	None	None	N
P/F	0.6487	likely_pathogenic	0.7395	pathogenic	-1.205	Destabilizing	0.991	D	0.878	deleterious	None	None	None	None	N
P/G	0.5382	ambiguous	0.6021	pathogenic	-2.178	Highly Destabilizing	0.992	D	0.828	deleterious	None	None	None	None	N
P/H	0.3381	likely_benign	0.4008	ambiguous	-1.664	Destabilizing	0.999	D	0.867	deleterious	N	0.518980642	None	None	N
P/I	0.2686	likely_benign	0.3197	benign	-0.716	Destabilizing	0.968	D	0.831	deleterious	None	None	None	None	N
P/K	0.4284	ambiguous	0.466	ambiguous	-1.597	Destabilizing	0.992	D	0.828	deleterious	None	None	None	None	N
P/L	0.1423	likely_benign	0.177	benign	-0.716	Destabilizing	0.085	N	0.567	neutral	D	0.525057028	None	None	N
P/M	0.3162	likely_benign	0.3619	ambiguous	-0.571	Destabilizing	0.996	D	0.871	deleterious	None	None	None	None	N
P/N	0.554	ambiguous	0.6358	pathogenic	-1.569	Destabilizing	0.997	D	0.887	deleterious	None	None	None	None	N
P/Q	0.2065	likely_benign	0.243	benign	-1.608	Destabilizing	0.997	D	0.873	deleterious	None	None	None	None	N
P/R	0.3347	likely_benign	0.385	ambiguous	-1.151	Destabilizing	0.989	D	0.884	deleterious	N	0.499292998	None	None	N
P/S	0.1844	likely_benign	0.2253	benign	-2.107	Highly Destabilizing	0.989	D	0.808	deleterious	N	0.492620727	None	None	N
P/T	0.1405	likely_benign	0.1744	benign	-1.884	Destabilizing	0.978	D	0.772	deleterious	N	0.502090928	None	None	N
P/V	0.1957	likely_benign	0.2206	benign	-1.038	Destabilizing	0.968	D	0.773	deleterious	None	None	None	None	N
P/W	0.8721	likely_pathogenic	0.9044	pathogenic	-1.508	Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
P/Y	0.642	likely_pathogenic	0.7164	pathogenic	-1.184	Destabilizing	0.998	D	0.869	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.