TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2934	9025;9026;9027	chr2:178769781;178769780;178769779	chr2:179634508;179634507;179634506
N2AB	2934	9025;9026;9027	chr2:178769781;178769780;178769779	chr2:179634508;179634507;179634506
N2A	2934	9025;9026;9027	chr2:178769781;178769780;178769779	chr2:179634508;179634507;179634506
N2B	2888	8887;8888;8889	chr2:178769781;178769780;178769779	chr2:179634508;179634507;179634506
Novex-1	2888	8887;8888;8889	chr2:178769781;178769780;178769779	chr2:179634508;179634507;179634506
Novex-2	2888	8887;8888;8889	chr2:178769781;178769780;178769779	chr2:179634508;179634507;179634506
Novex-3	2934	9025;9026;9027	chr2:178769781;178769780;178769779	chr2:179634508;179634507;179634506

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-19
• Domain position: 53
• Structural Position: 134
• Q(SASA): 0.1515
• 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
K/R	rs2091195170	None	0.64	N	0.229	0.341	0.273070737957	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	6.17284E-04	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
K/A	0.9712	likely_pathogenic	0.9207	pathogenic	-0.799	Destabilizing	0.998	D	0.587	neutral	None	None	None	None	N
K/C	0.9643	likely_pathogenic	0.9309	pathogenic	-0.785	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
K/D	0.9881	likely_pathogenic	0.9605	pathogenic	-0.136	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
K/E	0.9512	likely_pathogenic	0.8416	pathogenic	0.02	Stabilizing	0.996	D	0.568	neutral	N	0.518150283	None	None	N
K/F	0.9923	likely_pathogenic	0.9833	pathogenic	-0.324	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
K/G	0.9755	likely_pathogenic	0.9307	pathogenic	-1.203	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
K/H	0.8363	likely_pathogenic	0.737	pathogenic	-1.412	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
K/I	0.9609	likely_pathogenic	0.9095	pathogenic	0.27	Stabilizing	1.0	D	0.761	deleterious	D	0.590853903	None	None	N
K/L	0.9061	likely_pathogenic	0.8325	pathogenic	0.27	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
K/M	0.8408	likely_pathogenic	0.703	pathogenic	0.073	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
K/N	0.9357	likely_pathogenic	0.8388	pathogenic	-0.68	Destabilizing	0.999	D	0.657	neutral	N	0.513826528	None	None	N
K/P	0.9818	likely_pathogenic	0.9609	pathogenic	-0.057	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
K/Q	0.7439	likely_pathogenic	0.5423	ambiguous	-0.661	Destabilizing	0.999	D	0.661	neutral	N	0.516935427	None	None	N
K/R	0.1935	likely_benign	0.1481	benign	-0.661	Destabilizing	0.64	D	0.229	neutral	N	0.467651666	None	None	N
K/S	0.9744	likely_pathogenic	0.9199	pathogenic	-1.396	Destabilizing	0.998	D	0.606	neutral	None	None	None	None	N
K/T	0.889	likely_pathogenic	0.725	pathogenic	-1.015	Destabilizing	0.999	D	0.675	prob.neutral	N	0.507813405	None	None	N
K/V	0.9521	likely_pathogenic	0.8926	pathogenic	-0.057	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
K/W	0.9905	likely_pathogenic	0.9797	pathogenic	-0.183	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
K/Y	0.9665	likely_pathogenic	0.9425	pathogenic	0.099	Stabilizing	1.0	D	0.755	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.