TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31923	95992;95993;95994	chr2:178544462;178544461;178544460	chr2:179409189;179409188;179409187
N2AB	30282	91069;91070;91071	chr2:178544462;178544461;178544460	chr2:179409189;179409188;179409187
N2A	29355	88288;88289;88290	chr2:178544462;178544461;178544460	chr2:179409189;179409188;179409187
N2B	22858	68797;68798;68799	chr2:178544462;178544461;178544460	chr2:179409189;179409188;179409187
Novex-1	22983	69172;69173;69174	chr2:178544462;178544461;178544460	chr2:179409189;179409188;179409187
Novex-2	23050	69373;69374;69375	chr2:178544462;178544461;178544460	chr2:179409189;179409188;179409187
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: Fn3-121
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.3605
• 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	0.969	N	0.509	0.233	0.272639205421	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

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	0.3895	ambiguous	0.331	benign	-0.224	Destabilizing	0.953	D	0.535	neutral	None	None	None	None	N
K/C	0.7489	likely_pathogenic	0.6946	pathogenic	0.008	Stabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
K/D	0.7428	likely_pathogenic	0.66	pathogenic	-0.157	Destabilizing	0.998	D	0.697	prob.neutral	None	None	None	None	N
K/E	0.2907	likely_benign	0.2313	benign	-0.088	Destabilizing	0.969	D	0.509	neutral	N	0.499564967	None	None	N
K/F	0.8712	likely_pathogenic	0.8116	pathogenic	-0.007	Destabilizing	0.986	D	0.78	deleterious	None	None	None	None	N
K/G	0.5173	ambiguous	0.4472	ambiguous	-0.551	Destabilizing	0.993	D	0.641	neutral	None	None	None	None	N
K/H	0.4431	ambiguous	0.3685	ambiguous	-1.005	Destabilizing	0.999	D	0.671	neutral	None	None	None	None	N
K/I	0.509	ambiguous	0.4183	ambiguous	0.604	Stabilizing	0.964	D	0.745	deleterious	N	0.492866854	None	None	N
K/L	0.4809	ambiguous	0.3929	ambiguous	0.604	Stabilizing	0.778	D	0.526	neutral	None	None	None	None	N
K/M	0.3719	ambiguous	0.2929	benign	0.491	Stabilizing	0.807	D	0.495	neutral	None	None	None	None	N
K/N	0.6201	likely_pathogenic	0.5099	ambiguous	-0.014	Destabilizing	0.997	D	0.659	neutral	N	0.509744675	None	None	N
K/P	0.6275	likely_pathogenic	0.5958	pathogenic	0.358	Stabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	N
K/Q	0.179	likely_benign	0.1534	benign	-0.096	Destabilizing	0.991	D	0.659	neutral	N	0.471773632	None	None	N
K/R	0.0771	likely_benign	0.0756	benign	-0.463	Destabilizing	0.969	D	0.491	neutral	N	0.504242855	None	None	N
K/S	0.49	ambiguous	0.399	ambiguous	-0.481	Destabilizing	0.976	D	0.552	neutral	None	None	None	None	N
K/T	0.2938	likely_benign	0.2215	benign	-0.232	Destabilizing	0.982	D	0.651	neutral	N	0.46793529	None	None	N
K/V	0.459	ambiguous	0.3704	ambiguous	0.358	Stabilizing	0.91	D	0.608	neutral	None	None	None	None	N
K/W	0.8385	likely_pathogenic	0.7962	pathogenic	0.021	Stabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
K/Y	0.7435	likely_pathogenic	0.6661	pathogenic	0.296	Stabilizing	0.993	D	0.751	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.