TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3867	11824;11825;11826	chr2:178741634;178741633;178741632	chr2:179606361;179606360;179606359
N2AB	3550	10873;10874;10875	chr2:178741634;178741633;178741632	chr2:179606361;179606360;179606359
N2A	None	None	chr2:None	chr2:None
N2B	3504	10735;10736;10737	chr2:178741634;178741633;178741632	chr2:179606361;179606360;179606359
Novex-1	3629	11110;11111;11112	chr2:178741634;178741633;178741632	chr2:179606361;179606360;179606359
Novex-2	3696	11311;11312;11313	chr2:178741634;178741633;178741632	chr2:179606361;179606360;179606359
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: Ig-27
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.3136
• 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	rs769510047	-0.191	0.071	N	0.162	0.137	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
K/R	rs769510047	-0.191	0.071	N	0.162	0.137	None	gnomAD-4.0.0	3.18239E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71628E-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	0.76	likely_pathogenic	0.7706	pathogenic	-0.851	Destabilizing	0.942	D	0.447	neutral	None	None	None	None	N
K/C	0.8686	likely_pathogenic	0.8885	pathogenic	-0.826	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
K/D	0.9132	likely_pathogenic	0.9091	pathogenic	-0.056	Destabilizing	0.996	D	0.531	neutral	None	None	None	None	N
K/E	0.4442	ambiguous	0.5106	ambiguous	0.142	Stabilizing	0.961	D	0.413	neutral	N	0.499830769	None	None	N
K/F	0.9519	likely_pathogenic	0.9541	pathogenic	-0.297	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
K/G	0.8791	likely_pathogenic	0.8734	pathogenic	-1.28	Destabilizing	0.97	D	0.489	neutral	None	None	None	None	N
K/H	0.5388	ambiguous	0.5683	pathogenic	-1.338	Destabilizing	1.0	D	0.619	neutral	None	None	None	None	N
K/I	0.6511	likely_pathogenic	0.6627	pathogenic	0.303	Stabilizing	0.989	D	0.666	neutral	N	0.517220834	None	None	N
K/L	0.6627	likely_pathogenic	0.668	pathogenic	0.303	Stabilizing	0.97	D	0.501	neutral	None	None	None	None	N
K/M	0.5245	ambiguous	0.5389	ambiguous	0.009	Stabilizing	1.0	D	0.616	neutral	None	None	None	None	N
K/N	0.7968	likely_pathogenic	0.7954	pathogenic	-0.706	Destabilizing	0.989	D	0.469	neutral	N	0.505371329	None	None	N
K/P	0.9848	likely_pathogenic	0.9777	pathogenic	-0.054	Destabilizing	0.996	D	0.595	neutral	None	None	None	None	N
K/Q	0.2875	likely_benign	0.3428	ambiguous	-0.58	Destabilizing	0.989	D	0.497	neutral	N	0.469678898	None	None	N
K/R	0.1218	likely_benign	0.1307	benign	-0.527	Destabilizing	0.071	N	0.162	neutral	N	0.474247147	None	None	N
K/S	0.7732	likely_pathogenic	0.7792	pathogenic	-1.454	Destabilizing	0.942	D	0.392	neutral	None	None	None	None	N
K/T	0.4101	ambiguous	0.4061	ambiguous	-1.01	Destabilizing	0.433	N	0.256	neutral	N	0.443499596	None	None	N
K/V	0.6507	likely_pathogenic	0.6511	pathogenic	-0.054	Destabilizing	0.983	D	0.513	neutral	None	None	None	None	N
K/W	0.9511	likely_pathogenic	0.9513	pathogenic	-0.165	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	N
K/Y	0.8442	likely_pathogenic	0.8551	pathogenic	0.126	Stabilizing	0.999	D	0.652	neutral	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.