TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21994	66205;66206;66207	chr2:178582476;178582475;178582474	chr2:179447203;179447202;179447201
N2AB	20353	61282;61283;61284	chr2:178582476;178582475;178582474	chr2:179447203;179447202;179447201
N2A	19426	58501;58502;58503	chr2:178582476;178582475;178582474	chr2:179447203;179447202;179447201
N2B	12929	39010;39011;39012	chr2:178582476;178582475;178582474	chr2:179447203;179447202;179447201
Novex-1	13054	39385;39386;39387	chr2:178582476;178582475;178582474	chr2:179447203;179447202;179447201
Novex-2	13121	39586;39587;39588	chr2:178582476;178582475;178582474	chr2:179447203;179447202;179447201
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-47
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1064
• 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/E	None	None	0.011	N	0.345	0.094	0.141422826196	gnomAD-4.0.0	1.20036E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31255E-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	0.8869	likely_pathogenic	0.8465	pathogenic	-0.927	Destabilizing	0.892	D	0.695	prob.neutral	N	0.517286723	None	None	N
D/C	0.9753	likely_pathogenic	0.9569	pathogenic	-0.252	Destabilizing	0.999	D	0.776	deleterious	None	None	None	None	N
D/E	0.5551	ambiguous	0.5001	ambiguous	-0.664	Destabilizing	0.011	N	0.345	neutral	N	0.318209102	None	None	N
D/F	0.9527	likely_pathogenic	0.9338	pathogenic	-0.728	Destabilizing	0.996	D	0.81	deleterious	None	None	None	None	N
D/G	0.9372	likely_pathogenic	0.9115	pathogenic	-1.333	Destabilizing	0.892	D	0.699	prob.neutral	N	0.518500231	None	None	N
D/H	0.9043	likely_pathogenic	0.8471	pathogenic	-0.686	Destabilizing	0.995	D	0.747	deleterious	N	0.468152781	None	None	N
D/I	0.9694	likely_pathogenic	0.9486	pathogenic	0.201	Stabilizing	0.987	D	0.815	deleterious	None	None	None	None	N
D/K	0.9793	likely_pathogenic	0.9721	pathogenic	-0.927	Destabilizing	0.845	D	0.685	prob.neutral	None	None	None	None	N
D/L	0.9387	likely_pathogenic	0.9222	pathogenic	0.201	Stabilizing	0.975	D	0.765	deleterious	None	None	None	None	N
D/M	0.9804	likely_pathogenic	0.9692	pathogenic	0.841	Stabilizing	0.999	D	0.788	deleterious	None	None	None	None	N
D/N	0.7014	likely_pathogenic	0.6371	pathogenic	-1.171	Destabilizing	0.892	D	0.696	prob.neutral	N	0.49570073	None	None	N
D/P	0.9996	likely_pathogenic	0.9993	pathogenic	-0.155	Destabilizing	0.987	D	0.716	prob.delet.	None	None	None	None	N
D/Q	0.9145	likely_pathogenic	0.8746	pathogenic	-0.826	Destabilizing	0.95	D	0.731	prob.delet.	None	None	None	None	N
D/R	0.9804	likely_pathogenic	0.9718	pathogenic	-0.932	Destabilizing	0.975	D	0.703	prob.neutral	None	None	None	None	N
D/S	0.7473	likely_pathogenic	0.6758	pathogenic	-1.781	Destabilizing	0.916	D	0.656	neutral	None	None	None	None	N
D/T	0.9403	likely_pathogenic	0.9078	pathogenic	-1.392	Destabilizing	0.975	D	0.717	prob.delet.	None	None	None	None	N
D/V	0.9277	likely_pathogenic	0.8894	pathogenic	-0.155	Destabilizing	0.983	D	0.761	deleterious	N	0.51026475	None	None	N
D/W	0.9899	likely_pathogenic	0.9817	pathogenic	-0.904	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
D/Y	0.8197	likely_pathogenic	0.7355	pathogenic	-0.545	Destabilizing	0.994	D	0.811	deleterious	N	0.473343945	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.