TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2731	8416;8417;8418	chr2:178770601;178770600;178770599	chr2:179635328;179635327;179635326
N2AB	2731	8416;8417;8418	chr2:178770601;178770600;178770599	chr2:179635328;179635327;179635326
N2A	2731	8416;8417;8418	chr2:178770601;178770600;178770599	chr2:179635328;179635327;179635326
N2B	2685	8278;8279;8280	chr2:178770601;178770600;178770599	chr2:179635328;179635327;179635326
Novex-1	2685	8278;8279;8280	chr2:178770601;178770600;178770599	chr2:179635328;179635327;179635326
Novex-2	2685	8278;8279;8280	chr2:178770601;178770600;178770599	chr2:179635328;179635327;179635326
Novex-3	2731	8416;8417;8418	chr2:178770601;178770600;178770599	chr2:179635328;179635327;179635326

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-17
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.2679
• 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/A	rs2091318582	None	0.76	D	0.371	0.323	0.320256813643	gnomAD-4.0.0	1.59055E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85649E-06	0	0
T/I	None	None	0.991	D	0.591	0.675	0.646977041325	gnomAD-4.0.0	1.59057E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85649E-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
T/A	0.3108	likely_benign	0.4494	ambiguous	-0.704	Destabilizing	0.76	D	0.371	neutral	D	0.559990502	None	None	N
T/C	0.8972	likely_pathogenic	0.9565	pathogenic	-0.354	Destabilizing	0.999	D	0.591	neutral	None	None	None	None	N
T/D	0.7008	likely_pathogenic	0.841	pathogenic	-0.373	Destabilizing	0.986	D	0.517	neutral	None	None	None	None	N
T/E	0.7747	likely_pathogenic	0.9	pathogenic	-0.355	Destabilizing	0.986	D	0.526	neutral	None	None	None	None	N
T/F	0.8152	likely_pathogenic	0.9199	pathogenic	-0.61	Destabilizing	0.998	D	0.607	neutral	None	None	None	None	N
T/G	0.6511	likely_pathogenic	0.7712	pathogenic	-0.994	Destabilizing	0.91	D	0.475	neutral	None	None	None	None	N
T/H	0.7337	likely_pathogenic	0.8726	pathogenic	-1.257	Destabilizing	0.999	D	0.602	neutral	None	None	None	None	N
T/I	0.7433	likely_pathogenic	0.8785	pathogenic	-0.015	Destabilizing	0.991	D	0.591	neutral	D	0.561514846	None	None	N
T/K	0.817	likely_pathogenic	0.9291	pathogenic	-0.881	Destabilizing	0.982	D	0.523	neutral	D	0.558310477	None	None	N
T/L	0.4185	ambiguous	0.602	pathogenic	-0.015	Destabilizing	0.953	D	0.475	neutral	None	None	None	None	N
T/M	0.3067	likely_benign	0.4691	ambiguous	0.194	Stabilizing	0.999	D	0.583	neutral	None	None	None	None	N
T/N	0.2932	likely_benign	0.4224	ambiguous	-0.788	Destabilizing	0.986	D	0.483	neutral	None	None	None	None	N
T/P	0.5924	likely_pathogenic	0.7765	pathogenic	-0.212	Destabilizing	0.991	D	0.588	neutral	D	0.564338338	None	None	N
T/Q	0.6855	likely_pathogenic	0.8434	pathogenic	-0.868	Destabilizing	0.993	D	0.584	neutral	None	None	None	None	N
T/R	0.7422	likely_pathogenic	0.8918	pathogenic	-0.681	Destabilizing	0.982	D	0.587	neutral	D	0.602766267	None	None	N
T/S	0.1675	likely_benign	0.206	benign	-1.01	Destabilizing	0.17	N	0.172	neutral	N	0.450720272	None	None	N
T/V	0.6315	likely_pathogenic	0.7749	pathogenic	-0.212	Destabilizing	0.953	D	0.408	neutral	None	None	None	None	N
T/W	0.9481	likely_pathogenic	0.9781	pathogenic	-0.623	Destabilizing	0.999	D	0.621	neutral	None	None	None	None	N
T/Y	0.8249	likely_pathogenic	0.9251	pathogenic	-0.405	Destabilizing	0.998	D	0.611	neutral	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.