TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28859	86800;86801;86802	chr2:178559557;178559556;178559555	chr2:179424284;179424283;179424282
N2AB	27218	81877;81878;81879	chr2:178559557;178559556;178559555	chr2:179424284;179424283;179424282
N2A	26291	79096;79097;79098	chr2:178559557;178559556;178559555	chr2:179424284;179424283;179424282
N2B	19794	59605;59606;59607	chr2:178559557;178559556;178559555	chr2:179424284;179424283;179424282
Novex-1	19919	59980;59981;59982	chr2:178559557;178559556;178559555	chr2:179424284;179424283;179424282
Novex-2	19986	60181;60182;60183	chr2:178559557;178559556;178559555	chr2:179424284;179424283;179424282
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: Fn3-98
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.3429
• 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/E	rs1165101738	-0.189	0.675	N	0.473	0.165	0.255270683199	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
K/E	rs1165101738	-0.189	0.675	N	0.473	0.165	0.255270683199	gnomAD-4.0.0	1.36842E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99483E-07	1.15945E-05	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	0.4867	ambiguous	0.51	ambiguous	-0.256	Destabilizing	0.901	D	0.533	neutral	None	None	None	None	N
K/C	0.7742	likely_pathogenic	0.7781	pathogenic	-0.347	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
K/D	0.8492	likely_pathogenic	0.8649	pathogenic	-0.045	Destabilizing	0.97	D	0.703	prob.neutral	None	None	None	None	N
K/E	0.3993	ambiguous	0.42	ambiguous	-0.028	Destabilizing	0.675	D	0.473	neutral	N	0.493908431	None	None	N
K/F	0.9218	likely_pathogenic	0.9255	pathogenic	-0.442	Destabilizing	0.997	D	0.795	deleterious	None	None	None	None	N
K/G	0.5588	ambiguous	0.5703	pathogenic	-0.497	Destabilizing	0.97	D	0.661	neutral	None	None	None	None	N
K/H	0.5042	ambiguous	0.5098	ambiguous	-0.915	Destabilizing	0.99	D	0.684	prob.neutral	None	None	None	None	N
K/I	0.6737	likely_pathogenic	0.7098	pathogenic	0.311	Stabilizing	0.591	D	0.805	deleterious	N	0.491385597	None	None	N
K/L	0.579	likely_pathogenic	0.5989	pathogenic	0.311	Stabilizing	0.485	N	0.661	neutral	None	None	None	None	N
K/M	0.4504	ambiguous	0.4719	ambiguous	0.361	Stabilizing	0.989	D	0.677	prob.neutral	None	None	None	None	N
K/N	0.719	likely_pathogenic	0.749	pathogenic	0.067	Stabilizing	0.96	D	0.664	neutral	N	0.50866724	None	None	N
K/P	0.7983	likely_pathogenic	0.8233	pathogenic	0.151	Stabilizing	0.985	D	0.692	prob.neutral	None	None	None	None	N
K/Q	0.2236	likely_benign	0.2326	benign	-0.217	Destabilizing	0.746	D	0.668	neutral	N	0.519326951	None	None	N
K/R	0.0697	likely_benign	0.0707	benign	-0.14	Destabilizing	0.004	N	0.191	neutral	N	0.455488903	None	None	N
K/S	0.6117	likely_pathogenic	0.6389	pathogenic	-0.535	Destabilizing	0.901	D	0.578	neutral	None	None	None	None	N
K/T	0.4015	ambiguous	0.4399	ambiguous	-0.357	Destabilizing	0.879	D	0.655	neutral	N	0.515515854	None	None	N
K/V	0.5653	likely_pathogenic	0.599	pathogenic	0.151	Stabilizing	0.554	D	0.737	prob.delet.	None	None	None	None	N
K/W	0.8521	likely_pathogenic	0.8547	pathogenic	-0.335	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
K/Y	0.8249	likely_pathogenic	0.8294	pathogenic	0.017	Stabilizing	0.902	D	0.769	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.