TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24307	73144;73145;73146	chr2:178573213;178573212;178573211	chr2:179437940;179437939;179437938
N2AB	22666	68221;68222;68223	chr2:178573213;178573212;178573211	chr2:179437940;179437939;179437938
N2A	21739	65440;65441;65442	chr2:178573213;178573212;178573211	chr2:179437940;179437939;179437938
N2B	15242	45949;45950;45951	chr2:178573213;178573212;178573211	chr2:179437940;179437939;179437938
Novex-1	15367	46324;46325;46326	chr2:178573213;178573212;178573211	chr2:179437940;179437939;179437938
Novex-2	15434	46525;46526;46527	chr2:178573213;178573212;178573211	chr2:179437940;179437939;179437938
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-64
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.3935
• 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
A/T	rs774999975	-0.7	0.003	N	0.307	0.06	0.15556083564	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/T	rs774999975	-0.7	0.003	N	0.307	0.06	0.15556083564	gnomAD-4.0.0	6.57454E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.4705E-05	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
A/C	0.3273	likely_benign	0.3078	benign	-0.795	Destabilizing	0.991	D	0.565	neutral	None	None	None	None	I
A/D	0.1703	likely_benign	0.1314	benign	-1.015	Destabilizing	0.39	N	0.672	neutral	None	None	None	None	I
A/E	0.1296	likely_benign	0.1046	benign	-1.163	Destabilizing	0.003	N	0.33	neutral	N	0.326425941	None	None	I
A/F	0.2258	likely_benign	0.2025	benign	-1.246	Destabilizing	0.818	D	0.654	neutral	None	None	None	None	I
A/G	0.1154	likely_benign	0.1092	benign	-0.808	Destabilizing	0.491	N	0.424	neutral	N	0.463510953	None	None	I
A/H	0.2758	likely_benign	0.237	benign	-0.821	Destabilizing	0.901	D	0.639	neutral	None	None	None	None	I
A/I	0.1222	likely_benign	0.1116	benign	-0.646	Destabilizing	0.39	N	0.595	neutral	None	None	None	None	I
A/K	0.2045	likely_benign	0.1563	benign	-0.995	Destabilizing	0.004	N	0.382	neutral	None	None	None	None	I
A/L	0.0848	likely_benign	0.0808	benign	-0.646	Destabilizing	0.004	N	0.316	neutral	None	None	None	None	I
A/M	0.1244	likely_benign	0.1174	benign	-0.434	Destabilizing	0.818	D	0.607	neutral	None	None	None	None	I
A/N	0.1395	likely_benign	0.125	benign	-0.601	Destabilizing	0.561	D	0.708	prob.delet.	None	None	None	None	I
A/P	0.0935	likely_benign	0.0895	benign	-0.633	Destabilizing	0.873	D	0.667	neutral	N	0.390762634	None	None	I
A/Q	0.1633	likely_benign	0.1418	benign	-0.945	Destabilizing	0.047	N	0.317	neutral	None	None	None	None	I
A/R	0.246	likely_benign	0.1874	benign	-0.419	Destabilizing	0.39	N	0.678	prob.neutral	None	None	None	None	I
A/S	0.0789	likely_benign	0.0769	benign	-0.801	Destabilizing	0.166	N	0.433	neutral	N	0.478288405	None	None	I
A/T	0.069	likely_benign	0.0675	benign	-0.88	Destabilizing	0.003	N	0.307	neutral	N	0.438153936	None	None	I
A/V	0.0766	likely_benign	0.0715	benign	-0.633	Destabilizing	0.013	N	0.213	neutral	N	0.470650356	None	None	I
A/W	0.5724	likely_pathogenic	0.5171	ambiguous	-1.369	Destabilizing	0.991	D	0.673	neutral	None	None	None	None	I
A/Y	0.2913	likely_benign	0.2611	benign	-1.052	Destabilizing	0.965	D	0.653	neutral	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.