TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16713	50362;50363;50364	chr2:178612388;178612387;178612386	chr2:179477115;179477114;179477113
N2AB	15072	45439;45440;45441	chr2:178612388;178612387;178612386	chr2:179477115;179477114;179477113
N2A	14145	42658;42659;42660	chr2:178612388;178612387;178612386	chr2:179477115;179477114;179477113
N2B	7648	23167;23168;23169	chr2:178612388;178612387;178612386	chr2:179477115;179477114;179477113
Novex-1	7773	23542;23543;23544	chr2:178612388;178612387;178612386	chr2:179477115;179477114;179477113
Novex-2	7840	23743;23744;23745	chr2:178612388;178612387;178612386	chr2:179477115;179477114;179477113
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-9
• Domain position: 63
• Structural Position: 94
• Q(SASA): 0.3704
• 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
T/I	rs2056496324	None	0.782	D	0.712	0.303	0.56380075071	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
T/I	rs2056496324	None	0.782	D	0.712	0.303	0.56380075071	gnomAD-4.0.0	6.58233E-06	None	None	None	None	N	None	0	6.55824E-05	None	0	0	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
T/A	0.129	likely_benign	0.1438	benign	-0.545	Destabilizing	0.013	N	0.243	neutral	N	0.504753745	None	None	N
T/C	0.5999	likely_pathogenic	0.6951	pathogenic	-0.33	Destabilizing	0.973	D	0.711	prob.delet.	None	None	None	None	N
T/D	0.7184	likely_pathogenic	0.8256	pathogenic	0.102	Stabilizing	0.826	D	0.669	neutral	None	None	None	None	N
T/E	0.6735	likely_pathogenic	0.7524	pathogenic	0.058	Stabilizing	0.404	N	0.605	neutral	None	None	None	None	N
T/F	0.3686	ambiguous	0.4686	ambiguous	-0.818	Destabilizing	0.906	D	0.767	deleterious	None	None	None	None	N
T/G	0.2998	likely_benign	0.3676	ambiguous	-0.739	Destabilizing	0.404	N	0.584	neutral	None	None	None	None	N
T/H	0.4755	ambiguous	0.5526	ambiguous	-0.997	Destabilizing	0.973	D	0.747	deleterious	None	None	None	None	N
T/I	0.3035	likely_benign	0.3684	ambiguous	-0.139	Destabilizing	0.782	D	0.712	prob.delet.	D	0.548299866	None	None	N
T/K	0.5388	ambiguous	0.6679	pathogenic	-0.555	Destabilizing	0.404	N	0.618	neutral	None	None	None	None	N
T/L	0.1437	likely_benign	0.1731	benign	-0.139	Destabilizing	0.575	D	0.543	neutral	None	None	None	None	N
T/M	0.139	likely_benign	0.1382	benign	0.04	Stabilizing	0.991	D	0.713	prob.delet.	None	None	None	None	N
T/N	0.1875	likely_benign	0.2164	benign	-0.361	Destabilizing	0.642	D	0.549	neutral	N	0.472471974	None	None	N
T/P	0.3021	likely_benign	0.3975	ambiguous	-0.243	Destabilizing	0.879	D	0.724	prob.delet.	N	0.485417776	None	None	N
T/Q	0.4256	ambiguous	0.482	ambiguous	-0.553	Destabilizing	0.826	D	0.73	prob.delet.	None	None	None	None	N
T/R	0.5724	likely_pathogenic	0.6937	pathogenic	-0.28	Destabilizing	0.826	D	0.724	prob.delet.	None	None	None	None	N
T/S	0.1149	likely_benign	0.1194	benign	-0.613	Destabilizing	0.003	N	0.206	neutral	N	0.455335788	None	None	N
T/V	0.2195	likely_benign	0.26	benign	-0.243	Destabilizing	0.575	D	0.439	neutral	None	None	None	None	N
T/W	0.8211	likely_pathogenic	0.8926	pathogenic	-0.788	Destabilizing	0.991	D	0.728	prob.delet.	None	None	None	None	N
T/Y	0.4822	ambiguous	0.6121	pathogenic	-0.539	Destabilizing	0.967	D	0.764	deleterious	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.