TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15112	45559;45560;45561	chr2:178621490;178621489;178621488	chr2:179486217;179486216;179486215
N2AB	13471	40636;40637;40638	chr2:178621490;178621489;178621488	chr2:179486217;179486216;179486215
N2A	12544	37855;37856;37857	chr2:178621490;178621489;178621488	chr2:179486217;179486216;179486215
N2B	6047	18364;18365;18366	chr2:178621490;178621489;178621488	chr2:179486217;179486216;179486215
Novex-1	6172	18739;18740;18741	chr2:178621490;178621489;178621488	chr2:179486217;179486216;179486215
Novex-2	6239	18940;18941;18942	chr2:178621490;178621489;178621488	chr2:179486217;179486216;179486215
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-102
• Domain position: 82
• Structural Position: 173
• Q(SASA): 0.2856
• 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	None	None	0.959	N	0.447	0.11	0.325533332567	gnomAD-4.0.0	1.59441E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86338E-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	0.3069	likely_benign	0.3193	benign	-0.463	Destabilizing	0.759	D	0.423	neutral	None	None	None	None	N
K/C	0.6872	likely_pathogenic	0.7451	pathogenic	-0.526	Destabilizing	0.999	D	0.569	neutral	None	None	None	None	N
K/D	0.5447	ambiguous	0.5501	ambiguous	-0.019	Destabilizing	0.884	D	0.512	neutral	None	None	None	None	N
K/E	0.1467	likely_benign	0.1426	benign	0.047	Stabilizing	0.826	D	0.479	neutral	N	0.46655673	None	None	N
K/F	0.6329	likely_pathogenic	0.6719	pathogenic	-0.398	Destabilizing	0.997	D	0.589	neutral	None	None	None	None	N
K/G	0.5476	ambiguous	0.5531	ambiguous	-0.775	Destabilizing	0.863	D	0.481	neutral	None	None	None	None	N
K/H	0.2634	likely_benign	0.2965	benign	-1.15	Destabilizing	0.991	D	0.557	neutral	None	None	None	None	N
K/I	0.2262	likely_benign	0.2412	benign	0.315	Stabilizing	0.976	D	0.589	neutral	N	0.502924542	None	None	N
K/L	0.3016	likely_benign	0.3129	benign	0.315	Stabilizing	0.939	D	0.519	neutral	None	None	None	None	N
K/M	0.1689	likely_benign	0.1708	benign	0.294	Stabilizing	0.997	D	0.546	neutral	None	None	None	None	N
K/N	0.3177	likely_benign	0.3047	benign	-0.204	Destabilizing	0.061	N	0.195	neutral	N	0.448513504	None	None	N
K/P	0.8644	likely_pathogenic	0.8831	pathogenic	0.086	Stabilizing	0.991	D	0.57	neutral	None	None	None	None	N
K/Q	0.1212	likely_benign	0.1276	benign	-0.397	Destabilizing	0.959	D	0.534	neutral	N	0.487729273	None	None	N
K/R	0.0843	likely_benign	0.0879	benign	-0.375	Destabilizing	0.959	D	0.447	neutral	N	0.468229533	None	None	N
K/S	0.3549	ambiguous	0.3637	ambiguous	-0.883	Destabilizing	0.373	N	0.179	neutral	None	None	None	None	N
K/T	0.1305	likely_benign	0.137	benign	-0.627	Destabilizing	0.134	N	0.265	neutral	N	0.401068199	None	None	N
K/V	0.23	likely_benign	0.2542	benign	0.086	Stabilizing	0.939	D	0.549	neutral	None	None	None	None	N
K/W	0.7189	likely_pathogenic	0.7485	pathogenic	-0.251	Destabilizing	0.999	D	0.603	neutral	None	None	None	None	N
K/Y	0.5392	ambiguous	0.5667	pathogenic	0.068	Stabilizing	0.997	D	0.593	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.