TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28530	85813;85814;85815	chr2:178560544;178560543;178560542	chr2:179425271;179425270;179425269
N2AB	26889	80890;80891;80892	chr2:178560544;178560543;178560542	chr2:179425271;179425270;179425269
N2A	25962	78109;78110;78111	chr2:178560544;178560543;178560542	chr2:179425271;179425270;179425269
N2B	19465	58618;58619;58620	chr2:178560544;178560543;178560542	chr2:179425271;179425270;179425269
Novex-1	19590	58993;58994;58995	chr2:178560544;178560543;178560542	chr2:179425271;179425270;179425269
Novex-2	19657	59194;59195;59196	chr2:178560544;178560543;178560542	chr2:179425271;179425270;179425269
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-95
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.5054
• 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
K/E	None	None	0.999	N	0.557	0.39	0.311691414656	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	2.75482E-04	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
K/A	0.6496	likely_pathogenic	0.6516	pathogenic	-0.213	Destabilizing	0.999	D	0.577	neutral	None	None	None	None	I
K/C	0.8547	likely_pathogenic	0.8484	pathogenic	-0.321	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	I
K/D	0.8705	likely_pathogenic	0.8589	pathogenic	0.077	Stabilizing	1.0	D	0.625	neutral	None	None	None	None	I
K/E	0.454	ambiguous	0.4203	ambiguous	0.11	Stabilizing	0.999	D	0.557	neutral	N	0.520423029	None	None	I
K/F	0.9356	likely_pathogenic	0.9326	pathogenic	-0.341	Destabilizing	1.0	D	0.613	neutral	None	None	None	None	I
K/G	0.8104	likely_pathogenic	0.8026	pathogenic	-0.445	Destabilizing	1.0	D	0.555	neutral	None	None	None	None	I
K/H	0.5281	ambiguous	0.5199	ambiguous	-0.718	Destabilizing	1.0	D	0.581	neutral	None	None	None	None	I
K/I	0.5937	likely_pathogenic	0.5665	pathogenic	0.33	Stabilizing	1.0	D	0.631	neutral	N	0.476750836	None	None	I
K/L	0.6319	likely_pathogenic	0.6062	pathogenic	0.33	Stabilizing	1.0	D	0.555	neutral	None	None	None	None	I
K/M	0.4792	ambiguous	0.4632	ambiguous	0.11	Stabilizing	1.0	D	0.579	neutral	None	None	None	None	I
K/N	0.7774	likely_pathogenic	0.7558	pathogenic	0.06	Stabilizing	1.0	D	0.661	neutral	N	0.487978556	None	None	I
K/P	0.8398	likely_pathogenic	0.8092	pathogenic	0.177	Stabilizing	1.0	D	0.601	neutral	None	None	None	None	I
K/Q	0.2998	likely_benign	0.288	benign	-0.068	Destabilizing	1.0	D	0.659	neutral	N	0.509995391	None	None	I
K/R	0.1037	likely_benign	0.1021	benign	-0.144	Destabilizing	0.999	D	0.483	neutral	N	0.468152781	None	None	I
K/S	0.736	likely_pathogenic	0.7304	pathogenic	-0.47	Destabilizing	0.999	D	0.599	neutral	None	None	None	None	I
K/T	0.4327	ambiguous	0.4081	ambiguous	-0.269	Destabilizing	1.0	D	0.607	neutral	N	0.47421594	None	None	I
K/V	0.599	likely_pathogenic	0.5764	pathogenic	0.177	Stabilizing	1.0	D	0.597	neutral	None	None	None	None	I
K/W	0.9098	likely_pathogenic	0.9032	pathogenic	-0.326	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	I
K/Y	0.8343	likely_pathogenic	0.829	pathogenic	0.009	Stabilizing	1.0	D	0.609	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.