TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16536	49831;49832;49833	chr2:178613203;178613202;178613201	chr2:179477930;179477929;179477928
N2AB	14895	44908;44909;44910	chr2:178613203;178613202;178613201	chr2:179477930;179477929;179477928
N2A	13968	42127;42128;42129	chr2:178613203;178613202;178613201	chr2:179477930;179477929;179477928
N2B	7471	22636;22637;22638	chr2:178613203;178613202;178613201	chr2:179477930;179477929;179477928
Novex-1	7596	23011;23012;23013	chr2:178613203;178613202;178613201	chr2:179477930;179477929;179477928
Novex-2	7663	23212;23213;23214	chr2:178613203;178613202;178613201	chr2:179477930;179477929;179477928
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-7
• Domain position: 87
• Structural Position: 120
• Q(SASA): 0.2243
• 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/S	None	None	0.957	D	0.707	0.387	0.264547087235	gnomAD-4.0.0	6.85199E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00121E-07	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	0.1807	likely_benign	0.1438	benign	-1.46	Destabilizing	0.039	N	0.437	neutral	N	0.508400335	None	None	N
P/C	0.8959	likely_pathogenic	0.751	pathogenic	-0.949	Destabilizing	0.998	D	0.882	deleterious	None	None	None	None	N
P/D	0.9803	likely_pathogenic	0.9631	pathogenic	-1.161	Destabilizing	0.992	D	0.77	deleterious	None	None	None	None	N
P/E	0.9198	likely_pathogenic	0.8801	pathogenic	-1.209	Destabilizing	0.983	D	0.754	deleterious	None	None	None	None	N
P/F	0.8946	likely_pathogenic	0.7572	pathogenic	-1.263	Destabilizing	0.998	D	0.883	deleterious	None	None	None	None	N
P/G	0.8608	likely_pathogenic	0.7322	pathogenic	-1.719	Destabilizing	0.895	D	0.707	prob.neutral	None	None	None	None	N
P/H	0.8378	likely_pathogenic	0.6947	pathogenic	-1.162	Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
P/I	0.849	likely_pathogenic	0.7646	pathogenic	-0.868	Destabilizing	0.983	D	0.855	deleterious	None	None	None	None	N
P/K	0.9671	likely_pathogenic	0.9497	pathogenic	-1.146	Destabilizing	0.983	D	0.767	deleterious	None	None	None	None	N
P/L	0.6633	likely_pathogenic	0.6025	pathogenic	-0.868	Destabilizing	0.957	D	0.771	deleterious	D	0.66812914	None	None	N
P/M	0.8559	likely_pathogenic	0.7592	pathogenic	-0.622	Destabilizing	0.999	D	0.848	deleterious	None	None	None	None	N
P/N	0.9542	likely_pathogenic	0.9078	pathogenic	-0.856	Destabilizing	0.992	D	0.834	deleterious	None	None	None	None	N
P/Q	0.8327	likely_pathogenic	0.7537	pathogenic	-1.114	Destabilizing	0.989	D	0.818	deleterious	D	0.746024803	None	None	N
P/R	0.9268	likely_pathogenic	0.894	pathogenic	-0.539	Destabilizing	0.978	D	0.832	deleterious	D	0.67191602	None	None	N
P/S	0.6185	likely_pathogenic	0.4817	ambiguous	-1.354	Destabilizing	0.957	D	0.707	prob.neutral	D	0.614827789	None	None	N
P/T	0.6437	likely_pathogenic	0.5552	ambiguous	-1.303	Destabilizing	0.978	D	0.724	prob.delet.	D	0.650238128	None	None	N
P/V	0.7145	likely_pathogenic	0.5911	pathogenic	-1.031	Destabilizing	0.968	D	0.723	prob.delet.	None	None	None	None	N
P/W	0.9641	likely_pathogenic	0.9027	pathogenic	-1.345	Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
P/Y	0.8928	likely_pathogenic	0.7668	pathogenic	-1.096	Destabilizing	0.999	D	0.883	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.