TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25892	77899;77900;77901	chr2:178568458;178568457;178568456	chr2:179433185;179433184;179433183
N2AB	24251	72976;72977;72978	chr2:178568458;178568457;178568456	chr2:179433185;179433184;179433183
N2A	23324	70195;70196;70197	chr2:178568458;178568457;178568456	chr2:179433185;179433184;179433183
N2B	16827	50704;50705;50706	chr2:178568458;178568457;178568456	chr2:179433185;179433184;179433183
Novex-1	16952	51079;51080;51081	chr2:178568458;178568457;178568456	chr2:179433185;179433184;179433183
Novex-2	17019	51280;51281;51282	chr2:178568458;178568457;178568456	chr2:179433185;179433184;179433183
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-76
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.2848
• 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
D/V	None	None	0.97	N	0.725	0.317	0.529210848824	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
D/A	0.1707	likely_benign	0.1793	benign	-0.614	Destabilizing	0.698	D	0.647	neutral	N	0.504837501	None	None	N
D/C	0.7201	likely_pathogenic	0.7201	pathogenic	-0.339	Destabilizing	0.998	D	0.786	deleterious	None	None	None	None	N
D/E	0.2739	likely_benign	0.2763	benign	-0.631	Destabilizing	0.904	D	0.505	neutral	N	0.469136604	None	None	N
D/F	0.6743	likely_pathogenic	0.6821	pathogenic	-0.115	Destabilizing	0.993	D	0.746	deleterious	None	None	None	None	N
D/G	0.1316	likely_benign	0.1394	benign	-1.019	Destabilizing	0.002	N	0.267	neutral	N	0.34720107099999997	None	None	N
D/H	0.4338	ambiguous	0.4511	ambiguous	-0.553	Destabilizing	0.997	D	0.67	neutral	N	0.470911031	None	None	N
D/I	0.6949	likely_pathogenic	0.7161	pathogenic	0.48	Stabilizing	0.993	D	0.747	deleterious	None	None	None	None	N
D/K	0.704	likely_pathogenic	0.7265	pathogenic	-0.789	Destabilizing	0.956	D	0.619	neutral	None	None	None	None	N
D/L	0.444	ambiguous	0.4609	ambiguous	0.48	Stabilizing	0.978	D	0.728	prob.delet.	None	None	None	None	N
D/M	0.7011	likely_pathogenic	0.7109	pathogenic	0.991	Stabilizing	0.998	D	0.765	deleterious	None	None	None	None	N
D/N	0.1392	likely_benign	0.1496	benign	-1.156	Destabilizing	0.822	D	0.555	neutral	N	0.51509178	None	None	N
D/P	0.9491	likely_pathogenic	0.9537	pathogenic	0.141	Stabilizing	0.993	D	0.686	prob.neutral	None	None	None	None	N
D/Q	0.5355	ambiguous	0.5452	ambiguous	-0.942	Destabilizing	0.993	D	0.598	neutral	None	None	None	None	N
D/R	0.7645	likely_pathogenic	0.7746	pathogenic	-0.651	Destabilizing	0.978	D	0.731	prob.delet.	None	None	None	None	N
D/S	0.1132	likely_benign	0.1143	benign	-1.551	Destabilizing	0.86	D	0.538	neutral	None	None	None	None	N
D/T	0.3767	ambiguous	0.3974	ambiguous	-1.213	Destabilizing	0.978	D	0.614	neutral	None	None	None	None	N
D/V	0.4882	ambiguous	0.5082	ambiguous	0.141	Stabilizing	0.97	D	0.725	prob.delet.	N	0.4716715	None	None	N
D/W	0.9543	likely_pathogenic	0.9554	pathogenic	-0.007	Destabilizing	0.998	D	0.795	deleterious	None	None	None	None	N
D/Y	0.3395	likely_benign	0.3537	ambiguous	0.096	Stabilizing	0.99	D	0.746	deleterious	N	0.47141801	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.