TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27945	84058;84059;84060	chr2:178562299;178562298;178562297	chr2:179427026;179427025;179427024
N2AB	26304	79135;79136;79137	chr2:178562299;178562298;178562297	chr2:179427026;179427025;179427024
N2A	25377	76354;76355;76356	chr2:178562299;178562298;178562297	chr2:179427026;179427025;179427024
N2B	18880	56863;56864;56865	chr2:178562299;178562298;178562297	chr2:179427026;179427025;179427024
Novex-1	19005	57238;57239;57240	chr2:178562299;178562298;178562297	chr2:179427026;179427025;179427024
Novex-2	19072	57439;57440;57441	chr2:178562299;178562298;178562297	chr2:179427026;179427025;179427024
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-91
• Domain position: 83
• Structural Position: 118
• Q(SASA): 0.0953
• 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
S/R	None	None	1.0	D	0.781	0.505	0.455173453901	gnomAD-4.0.0	2.73762E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59824E-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
S/A	0.5097	ambiguous	0.5678	pathogenic	-0.653	Destabilizing	0.125	N	0.697	prob.neutral	None	None	None	None	N
S/C	0.7707	likely_pathogenic	0.7955	pathogenic	-0.665	Destabilizing	1.0	D	0.737	prob.delet.	D	0.549941551	None	None	N
S/D	0.987	likely_pathogenic	0.99	pathogenic	-1.448	Destabilizing	0.785	D	0.744	deleterious	None	None	None	None	N
S/E	0.9944	likely_pathogenic	0.995	pathogenic	-1.369	Destabilizing	0.912	D	0.759	deleterious	None	None	None	None	N
S/F	0.9942	likely_pathogenic	0.9952	pathogenic	-0.504	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
S/G	0.153	likely_benign	0.2022	benign	-0.973	Destabilizing	0.007	N	0.452	neutral	N	0.499671249	None	None	N
S/H	0.9904	likely_pathogenic	0.9908	pathogenic	-1.45	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
S/I	0.9911	likely_pathogenic	0.993	pathogenic	0.115	Stabilizing	0.999	D	0.821	deleterious	D	0.549688061	None	None	N
S/K	0.9983	likely_pathogenic	0.9985	pathogenic	-0.962	Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
S/L	0.9569	likely_pathogenic	0.9647	pathogenic	0.115	Stabilizing	0.998	D	0.795	deleterious	None	None	None	None	N
S/M	0.9722	likely_pathogenic	0.9786	pathogenic	0.25	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
S/N	0.9553	likely_pathogenic	0.9618	pathogenic	-1.255	Destabilizing	0.244	N	0.737	prob.delet.	D	0.548927593	None	None	N
S/P	0.9946	likely_pathogenic	0.9952	pathogenic	-0.106	Destabilizing	0.963	D	0.782	deleterious	None	None	None	None	N
S/Q	0.9926	likely_pathogenic	0.9934	pathogenic	-1.258	Destabilizing	0.99	D	0.778	deleterious	None	None	None	None	N
S/R	0.997	likely_pathogenic	0.9972	pathogenic	-0.981	Destabilizing	1.0	D	0.781	deleterious	D	0.531076827	None	None	N
S/T	0.745	likely_pathogenic	0.8123	pathogenic	-1.014	Destabilizing	0.05	N	0.714	prob.delet.	D	0.536557329	None	None	N
S/V	0.9855	likely_pathogenic	0.9892	pathogenic	-0.106	Destabilizing	0.997	D	0.816	deleterious	None	None	None	None	N
S/W	0.9934	likely_pathogenic	0.9933	pathogenic	-0.68	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
S/Y	0.9885	likely_pathogenic	0.9897	pathogenic	-0.347	Destabilizing	0.999	D	0.822	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.