TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7916	23971;23972;23973	chr2:178719746;178719745;178719744	chr2:179584473;179584472;179584471
N2AB	7599	23020;23021;23022	chr2:178719746;178719745;178719744	chr2:179584473;179584472;179584471
N2A	6672	20239;20240;20241	chr2:178719746;178719745;178719744	chr2:179584473;179584472;179584471
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-64
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.7438
• 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
P/R	rs764130233	0.367	0.467	D	0.411	0.544	0.503930629158	gnomAD-2.1.1	1.61E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	9.29E-05	1.78E-05	0
P/R	rs764130233	0.367	0.467	D	0.411	0.544	0.503930629158	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	9.43E-05	0	0	0	0
P/R	rs764130233	0.367	0.467	D	0.411	0.544	0.503930629158	gnomAD-4.0.0	2.29309E-05	None	None	None	None	I	None	0	0	None	0	0	None	2.3439E-04	0	1.69534E-05	0	3.20266E-05
P/S	rs1264639309	None	0.999	D	0.614	0.609	0.568535626052	gnomAD-4.0.0	1.59153E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02517E-05

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
P/A	0.5759	likely_pathogenic	0.6271	pathogenic	-0.32	Destabilizing	0.992	D	0.597	neutral	D	0.542034962	None	None	I
P/C	0.9688	likely_pathogenic	0.9744	pathogenic	-0.684	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
P/D	0.9328	likely_pathogenic	0.9449	pathogenic	-0.325	Destabilizing	0.999	D	0.607	neutral	None	None	None	None	I
P/E	0.8027	likely_pathogenic	0.8493	pathogenic	-0.447	Destabilizing	0.998	D	0.616	neutral	None	None	None	None	I
P/F	0.9814	likely_pathogenic	0.9814	pathogenic	-0.685	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	I
P/G	0.8663	likely_pathogenic	0.8732	pathogenic	-0.395	Destabilizing	0.999	D	0.598	neutral	None	None	None	None	I
P/H	0.8596	likely_pathogenic	0.8821	pathogenic	0.018	Stabilizing	1.0	D	0.622	neutral	None	None	None	None	I
P/I	0.912	likely_pathogenic	0.916	pathogenic	-0.272	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	I
P/K	0.8441	likely_pathogenic	0.8737	pathogenic	-0.35	Destabilizing	0.988	D	0.615	neutral	None	None	None	None	I
P/L	0.7023	likely_pathogenic	0.7385	pathogenic	-0.272	Destabilizing	0.998	D	0.647	neutral	D	0.625708311	None	None	I
P/M	0.8919	likely_pathogenic	0.9062	pathogenic	-0.475	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	I
P/N	0.926	likely_pathogenic	0.9366	pathogenic	-0.109	Destabilizing	0.999	D	0.605	neutral	None	None	None	None	I
P/Q	0.7564	likely_pathogenic	0.8013	pathogenic	-0.347	Destabilizing	0.998	D	0.589	neutral	D	0.576433046	None	None	I
P/R	0.7429	likely_pathogenic	0.7911	pathogenic	0.132	Stabilizing	0.467	N	0.411	neutral	D	0.609053176	None	None	I
P/S	0.7696	likely_pathogenic	0.8087	pathogenic	-0.419	Destabilizing	0.999	D	0.614	neutral	D	0.546300923	None	None	I
P/T	0.6123	likely_pathogenic	0.6504	pathogenic	-0.448	Destabilizing	0.999	D	0.611	neutral	D	0.612303482	None	None	I
P/V	0.8077	likely_pathogenic	0.8153	pathogenic	-0.258	Destabilizing	0.999	D	0.619	neutral	None	None	None	None	I
P/W	0.9825	likely_pathogenic	0.9854	pathogenic	-0.747	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
P/Y	0.9713	likely_pathogenic	0.9723	pathogenic	-0.457	Destabilizing	1.0	D	0.667	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.