TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17115	51568;51569;51570	chr2:178610183;178610182;178610181	chr2:179474910;179474909;179474908
N2AB	15474	46645;46646;46647	chr2:178610183;178610182;178610181	chr2:179474910;179474909;179474908
N2A	14547	43864;43865;43866	chr2:178610183;178610182;178610181	chr2:179474910;179474909;179474908
N2B	8050	24373;24374;24375	chr2:178610183;178610182;178610181	chr2:179474910;179474909;179474908
Novex-1	8175	24748;24749;24750	chr2:178610183;178610182;178610181	chr2:179474910;179474909;179474908
Novex-2	8242	24949;24950;24951	chr2:178610183;178610182;178610181	chr2:179474910;179474909;179474908
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-12
• Domain position: 69
• Structural Position: 102
• Q(SASA): 0.1931
• 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
G/D	rs796362520	None	0.709	N	0.715	0.216	0.233150807113	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56251E-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
G/A	0.1649	likely_benign	0.195	benign	-0.656	Destabilizing	0.41	N	0.433	neutral	N	0.444442403	None	None	N
G/C	0.3107	likely_benign	0.3693	ambiguous	-0.708	Destabilizing	0.023	N	0.559	neutral	N	0.447869497	None	None	N
G/D	0.8591	likely_pathogenic	0.8759	pathogenic	-1.68	Destabilizing	0.709	D	0.715	prob.delet.	N	0.506781728	None	None	N
G/E	0.747	likely_pathogenic	0.7978	pathogenic	-1.619	Destabilizing	0.764	D	0.719	prob.delet.	None	None	None	None	N
G/F	0.9031	likely_pathogenic	0.9302	pathogenic	-0.753	Destabilizing	0.98	D	0.715	prob.delet.	None	None	None	None	N
G/H	0.8063	likely_pathogenic	0.824	pathogenic	-1.731	Destabilizing	0.98	D	0.661	neutral	None	None	None	None	N
G/I	0.5855	likely_pathogenic	0.714	pathogenic	0.113	Stabilizing	0.866	D	0.729	prob.delet.	None	None	None	None	N
G/K	0.8887	likely_pathogenic	0.8969	pathogenic	-1.253	Destabilizing	0.764	D	0.719	prob.delet.	None	None	None	None	N
G/L	0.7408	likely_pathogenic	0.8082	pathogenic	0.113	Stabilizing	0.764	D	0.735	prob.delet.	None	None	None	None	N
G/M	0.6328	likely_pathogenic	0.7273	pathogenic	0.107	Stabilizing	0.993	D	0.689	prob.neutral	None	None	None	None	N
G/N	0.5511	ambiguous	0.6225	pathogenic	-1.121	Destabilizing	0.764	D	0.723	prob.delet.	None	None	None	None	N
G/P	0.9967	likely_pathogenic	0.998	pathogenic	-0.099	Destabilizing	0.866	D	0.713	prob.delet.	None	None	None	None	N
G/Q	0.6612	likely_pathogenic	0.701	pathogenic	-1.115	Destabilizing	0.866	D	0.698	prob.neutral	None	None	None	None	N
G/R	0.7906	likely_pathogenic	0.7978	pathogenic	-1.18	Destabilizing	0.83	D	0.709	prob.delet.	N	0.418333237	None	None	N
G/S	0.1373	likely_benign	0.1728	benign	-1.386	Destabilizing	0.004	N	0.32	neutral	N	0.414100853	None	None	N
G/T	0.2364	likely_benign	0.3427	ambiguous	-1.235	Destabilizing	0.764	D	0.707	prob.neutral	None	None	None	None	N
G/V	0.4082	ambiguous	0.5508	ambiguous	-0.099	Destabilizing	0.709	D	0.733	prob.delet.	N	0.42753151	None	None	N
G/W	0.8546	likely_pathogenic	0.8802	pathogenic	-1.445	Destabilizing	0.993	D	0.605	neutral	None	None	None	None	N
G/Y	0.8393	likely_pathogenic	0.8648	pathogenic	-0.888	Destabilizing	0.98	D	0.717	prob.delet.	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.