TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21049	63370;63371;63372	chr2:178588580;178588579;178588578	chr2:179453307;179453306;179453305
N2AB	19408	58447;58448;58449	chr2:178588580;178588579;178588578	chr2:179453307;179453306;179453305
N2A	18481	55666;55667;55668	chr2:178588580;178588579;178588578	chr2:179453307;179453306;179453305
N2B	11984	36175;36176;36177	chr2:178588580;178588579;178588578	chr2:179453307;179453306;179453305
Novex-1	12109	36550;36551;36552	chr2:178588580;178588579;178588578	chr2:179453307;179453306;179453305
Novex-2	12176	36751;36752;36753	chr2:178588580;178588579;178588578	chr2:179453307;179453306;179453305
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: Fn3-40
• Domain position: 87
• Structural Position: 120
• Q(SASA): 0.3514
• Predicted PPI site: I

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	rs1559560525	None	0.946	N	0.863	0.497	0.44731173	gnomAD-2.1.1	5.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.06E-05	0
P/R	rs1559560525	None	0.946	N	0.863	0.497	0.44731173	gnomAD-4.0.0	2.86209E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.69436E-06	0	0
P/S	None	None	0.898	N	0.741	0.371	0.27977628	gnomAD-4.0.0	1.77046E-06	None	None	None	None	I	None	0	0	None	0	2.80962E-05	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
P/A	0.0918	likely_benign	0.085	benign	-1.681	Destabilizing	0.016	N	0.432	neutral	N	0.5145344	None	None	I
P/C	0.5644	likely_pathogenic	0.518	ambiguous	-1.061	Destabilizing	0.994	D	0.859	deleterious	None	None	None	None	I
P/D	0.8777	likely_pathogenic	0.8435	pathogenic	-1.664	Destabilizing	0.979	D	0.826	deleterious	None	None	None	None	I
P/E	0.7542	likely_pathogenic	0.7079	pathogenic	-1.682	Destabilizing	0.959	D	0.803	deleterious	None	None	None	None	I
P/F	0.5525	ambiguous	0.5574	ambiguous	-1.331	Destabilizing	0.994	D	0.863	deleterious	None	None	None	None	I
P/G	0.6138	likely_pathogenic	0.532	ambiguous	-1.969	Destabilizing	0.769	D	0.75	deleterious	None	None	None	None	I
P/H	0.541	ambiguous	0.513	ambiguous	-1.372	Destabilizing	0.998	D	0.845	deleterious	None	None	None	None	I
P/I	0.5351	ambiguous	0.4744	ambiguous	-0.984	Destabilizing	0.959	D	0.85	deleterious	None	None	None	None	I
P/K	0.8784	likely_pathogenic	0.8373	pathogenic	-1.269	Destabilizing	0.959	D	0.822	deleterious	None	None	None	None	I
P/L	0.3343	likely_benign	0.3032	benign	-0.984	Destabilizing	0.898	D	0.787	deleterious	N	0.4953187	None	None	I
P/M	0.5114	ambiguous	0.4684	ambiguous	-0.749	Destabilizing	0.994	D	0.845	deleterious	None	None	None	None	I
P/N	0.7597	likely_pathogenic	0.698	pathogenic	-1.032	Destabilizing	0.979	D	0.864	deleterious	None	None	None	None	I
P/Q	0.5931	likely_pathogenic	0.5351	ambiguous	-1.286	Destabilizing	0.973	D	0.863	deleterious	N	0.51133627	None	None	I
P/R	0.7905	likely_pathogenic	0.7375	pathogenic	-0.666	Destabilizing	0.946	D	0.863	deleterious	N	0.4910792	None	None	I
P/S	0.2713	likely_benign	0.2303	benign	-1.524	Destabilizing	0.898	D	0.741	deleterious	N	0.47246796	None	None	I
P/T	0.2941	likely_benign	0.2462	benign	-1.449	Destabilizing	0.946	D	0.75	deleterious	N	0.49709314	None	None	I
P/V	0.3596	ambiguous	0.3137	benign	-1.184	Destabilizing	0.921	D	0.755	deleterious	None	None	None	None	I
P/W	0.8027	likely_pathogenic	0.7868	pathogenic	-1.442	Destabilizing	0.998	D	0.824	deleterious	None	None	None	None	I
P/Y	0.5954	likely_pathogenic	0.5716	pathogenic	-1.202	Destabilizing	0.998	D	0.864	deleterious	None	None	None	None	I

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.