TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24222	72889;72890;72891	chr2:178573468;178573467;178573466	chr2:179438195;179438194;179438193
N2AB	22581	67966;67967;67968	chr2:178573468;178573467;178573466	chr2:179438195;179438194;179438193
N2A	21654	65185;65186;65187	chr2:178573468;178573467;178573466	chr2:179438195;179438194;179438193
N2B	15157	45694;45695;45696	chr2:178573468;178573467;178573466	chr2:179438195;179438194;179438193
Novex-1	15282	46069;46070;46071	chr2:178573468;178573467;178573466	chr2:179438195;179438194;179438193
Novex-2	15349	46270;46271;46272	chr2:178573468;178573467;178573466	chr2:179438195;179438194;179438193
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-64
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.6427
• 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	None	None	0.049	N	0.463	0.161	0.256793551483	gnomAD-4.0.0	1.91061E-06	None	None	None	None	I	None	0	0	None	0	0	None	2.02151E-05	0	0	0	0
P/S	rs764364289	0.035	0.961	N	0.569	0.337	0.332133492242	gnomAD-2.1.1	5.85E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.18E-05	0
P/S	rs764364289	0.035	0.961	N	0.569	0.337	0.332133492242	gnomAD-4.0.0	2.94393E-06	None	None	None	None	I	None	0	0	None	0	2.60173E-05	None	0	1.8875E-04	9.38245E-07	0	1.78591E-05

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	0.1017	likely_benign	0.0957	benign	-0.286	Destabilizing	0.78	D	0.583	neutral	N	0.470587727	None	None	I
P/C	0.3485	ambiguous	0.3152	benign	-0.538	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	I
P/D	0.6487	likely_pathogenic	0.6052	pathogenic	0.056	Stabilizing	0.985	D	0.603	neutral	None	None	None	None	I
P/E	0.3599	ambiguous	0.3195	benign	-0.068	Destabilizing	0.971	D	0.569	neutral	None	None	None	None	I
P/F	0.3796	ambiguous	0.3283	benign	-0.701	Destabilizing	0.992	D	0.789	deleterious	None	None	None	None	I
P/G	0.4786	ambiguous	0.4383	ambiguous	-0.374	Destabilizing	0.985	D	0.532	neutral	None	None	None	None	I
P/H	0.2204	likely_benign	0.1969	benign	-0.051	Destabilizing	0.998	D	0.767	deleterious	N	0.496799966	None	None	I
P/I	0.1258	likely_benign	0.118	benign	-0.215	Destabilizing	0.943	D	0.673	prob.neutral	None	None	None	None	I
P/K	0.218	likely_benign	0.2021	benign	-0.028	Destabilizing	0.825	D	0.715	prob.delet.	None	None	None	None	I
P/L	0.0816	likely_benign	0.0753	benign	-0.215	Destabilizing	0.78	D	0.64	neutral	N	0.465400395	None	None	I
P/M	0.2025	likely_benign	0.1942	benign	-0.181	Destabilizing	0.996	D	0.76	deleterious	None	None	None	None	I
P/N	0.4168	ambiguous	0.3649	ambiguous	0.18	Stabilizing	0.985	D	0.833	deleterious	None	None	None	None	I
P/Q	0.1768	likely_benign	0.1569	benign	-0.083	Destabilizing	0.971	D	0.577	neutral	None	None	None	None	I
P/R	0.1765	likely_benign	0.1556	benign	0.397	Stabilizing	0.049	N	0.463	neutral	N	0.462780275	None	None	I
P/S	0.1836	likely_benign	0.1709	benign	-0.196	Destabilizing	0.961	D	0.569	neutral	N	0.490759578	None	None	I
P/T	0.1078	likely_benign	0.1055	benign	-0.222	Destabilizing	0.961	D	0.599	neutral	N	0.513383284	None	None	I
P/V	0.1076	likely_benign	0.1002	benign	-0.206	Destabilizing	0.064	N	0.362	neutral	None	None	None	None	I
P/W	0.6858	likely_pathogenic	0.619	pathogenic	-0.756	Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	I
P/Y	0.4425	ambiguous	0.3861	ambiguous	-0.409	Destabilizing	0.985	D	0.797	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.