TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27988	84187;84188;84189	chr2:178562170;178562169;178562168	chr2:179426897;179426896;179426895
N2AB	26347	79264;79265;79266	chr2:178562170;178562169;178562168	chr2:179426897;179426896;179426895
N2A	25420	76483;76484;76485	chr2:178562170;178562169;178562168	chr2:179426897;179426896;179426895
N2B	18923	56992;56993;56994	chr2:178562170;178562169;178562168	chr2:179426897;179426896;179426895
Novex-1	19048	57367;57368;57369	chr2:178562170;178562169;178562168	chr2:179426897;179426896;179426895
Novex-2	19115	57568;57569;57570	chr2:178562170;178562169;178562168	chr2:179426897;179426896;179426895
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-142
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.3203
• 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
G/E	rs267599033	None	0.056	D	0.424	0.73	0.476127810785	gnomAD-4.0.0	1.59299E-06	None	None	None	None	I	None	0	2.29232E-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
G/A	0.2446	likely_benign	0.2885	benign	-0.459	Destabilizing	0.099	N	0.334	neutral	D	0.537230347	None	None	I
G/C	0.653	likely_pathogenic	0.695	pathogenic	-0.787	Destabilizing	0.999	D	0.655	neutral	None	None	None	None	I
G/D	0.975	likely_pathogenic	0.9844	pathogenic	-0.843	Destabilizing	0.95	D	0.626	neutral	None	None	None	None	I
G/E	0.9749	likely_pathogenic	0.9853	pathogenic	-0.961	Destabilizing	0.056	N	0.424	neutral	D	0.630167647	None	None	I
G/F	0.9776	likely_pathogenic	0.9805	pathogenic	-0.951	Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	I
G/H	0.9894	likely_pathogenic	0.9926	pathogenic	-1.014	Destabilizing	0.997	D	0.609	neutral	None	None	None	None	I
G/I	0.908	likely_pathogenic	0.936	pathogenic	-0.332	Destabilizing	0.987	D	0.699	prob.neutral	None	None	None	None	I
G/K	0.9945	likely_pathogenic	0.9966	pathogenic	-1.171	Destabilizing	0.95	D	0.623	neutral	None	None	None	None	I
G/L	0.9306	likely_pathogenic	0.9433	pathogenic	-0.332	Destabilizing	0.975	D	0.694	prob.neutral	None	None	None	None	I
G/M	0.9557	likely_pathogenic	0.9663	pathogenic	-0.337	Destabilizing	0.999	D	0.654	neutral	None	None	None	None	I
G/N	0.9718	likely_pathogenic	0.9793	pathogenic	-0.724	Destabilizing	0.975	D	0.624	neutral	None	None	None	None	I
G/P	0.9944	likely_pathogenic	0.9964	pathogenic	-0.335	Destabilizing	0.073	N	0.427	neutral	None	None	None	None	I
G/Q	0.98	likely_pathogenic	0.9869	pathogenic	-0.961	Destabilizing	0.975	D	0.642	neutral	None	None	None	None	I
G/R	0.9809	likely_pathogenic	0.9881	pathogenic	-0.788	Destabilizing	0.967	D	0.635	neutral	D	0.633800123	None	None	I
G/S	0.4275	ambiguous	0.5333	ambiguous	-0.888	Destabilizing	0.845	D	0.567	neutral	None	None	None	None	I
G/T	0.7997	likely_pathogenic	0.8536	pathogenic	-0.937	Destabilizing	0.975	D	0.623	neutral	None	None	None	None	I
G/V	0.7942	likely_pathogenic	0.8524	pathogenic	-0.335	Destabilizing	0.967	D	0.697	prob.neutral	D	0.633800123	None	None	I
G/W	0.9737	likely_pathogenic	0.9812	pathogenic	-1.232	Destabilizing	0.999	D	0.58	neutral	None	None	None	None	I
G/Y	0.972	likely_pathogenic	0.9782	pathogenic	-0.856	Destabilizing	0.999	D	0.684	prob.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.