TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21380	64363;64364;64365	chr2:178586763;178586762;178586761	chr2:179451490;179451489;179451488
N2AB	19739	59440;59441;59442	chr2:178586763;178586762;178586761	chr2:179451490;179451489;179451488
N2A	18812	56659;56660;56661	chr2:178586763;178586762;178586761	chr2:179451490;179451489;179451488
N2B	12315	37168;37169;37170	chr2:178586763;178586762;178586761	chr2:179451490;179451489;179451488
Novex-1	12440	37543;37544;37545	chr2:178586763;178586762;178586761	chr2:179451490;179451489;179451488
Novex-2	12507	37744;37745;37746	chr2:178586763;178586762;178586761	chr2:179451490;179451489;179451488
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-43
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.3686
• 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	None	None	0.999	N	0.578	0.27	0.336647302497	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
K/R	rs2049068326	None	0.999	N	0.531	0.221	None	gnomAD-4.0.0	2.05359E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69947E-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
K/A	0.5091	ambiguous	0.3948	ambiguous	-0.157	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	N
K/C	0.839	likely_pathogenic	0.7874	pathogenic	-0.163	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
K/D	0.883	likely_pathogenic	0.8024	pathogenic	-0.142	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
K/E	0.4803	ambiguous	0.3476	ambiguous	-0.134	Destabilizing	0.999	D	0.578	neutral	N	0.491214843	None	None	N
K/F	0.97	likely_pathogenic	0.947	pathogenic	-0.395	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
K/G	0.5996	likely_pathogenic	0.4793	ambiguous	-0.391	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
K/H	0.6565	likely_pathogenic	0.5784	pathogenic	-0.882	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
K/I	0.7905	likely_pathogenic	0.6998	pathogenic	0.39	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
K/L	0.7531	likely_pathogenic	0.644	pathogenic	0.39	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
K/M	0.6082	likely_pathogenic	0.4836	ambiguous	0.484	Stabilizing	1.0	D	0.658	neutral	N	0.502083566	None	None	N
K/N	0.7873	likely_pathogenic	0.6546	pathogenic	0.136	Stabilizing	1.0	D	0.762	deleterious	N	0.508397881	None	None	N
K/P	0.8255	likely_pathogenic	0.7871	pathogenic	0.237	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
K/Q	0.2734	likely_benign	0.2157	benign	-0.144	Destabilizing	1.0	D	0.75	deleterious	N	0.520673745	None	None	N
K/R	0.0838	likely_benign	0.0814	benign	-0.125	Destabilizing	0.999	D	0.531	neutral	N	0.47488274	None	None	N
K/S	0.6585	likely_pathogenic	0.522	ambiguous	-0.394	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
K/T	0.5534	ambiguous	0.4137	ambiguous	-0.231	Destabilizing	1.0	D	0.723	prob.delet.	N	0.503664065	None	None	N
K/V	0.6725	likely_pathogenic	0.5692	pathogenic	0.237	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
K/W	0.9429	likely_pathogenic	0.9131	pathogenic	-0.334	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
K/Y	0.9102	likely_pathogenic	0.8586	pathogenic	0.032	Stabilizing	1.0	D	0.736	prob.delet.	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.