TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26636	80131;80132;80133	chr2:178566226;178566225;178566224	chr2:179430953;179430952;179430951
N2AB	24995	75208;75209;75210	chr2:178566226;178566225;178566224	chr2:179430953;179430952;179430951
N2A	24068	72427;72428;72429	chr2:178566226;178566225;178566224	chr2:179430953;179430952;179430951
N2B	17571	52936;52937;52938	chr2:178566226;178566225;178566224	chr2:179430953;179430952;179430951
Novex-1	17696	53311;53312;53313	chr2:178566226;178566225;178566224	chr2:179430953;179430952;179430951
Novex-2	17763	53512;53513;53514	chr2:178566226;178566225;178566224	chr2:179430953;179430952;179430951
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: Ig-138
• Domain position: 43
• Structural Position: 73
• Q(SASA): 0.4037
• 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	0.977	N	0.457	0.277	0.20549828249	gnomAD-4.0.0	1.59146E-06	None	None	None	None	N	None	0	0	None	0	2.77393E-05	None	0	0	0	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	0.5634	ambiguous	0.4667	ambiguous	-0.344	Destabilizing	0.983	D	0.524	neutral	None	None	None	None	N
K/C	0.7983	likely_pathogenic	0.7451	pathogenic	-0.239	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
K/D	0.7413	likely_pathogenic	0.6709	pathogenic	-0.299	Destabilizing	0.998	D	0.703	prob.neutral	None	None	None	None	N
K/E	0.4322	ambiguous	0.3534	ambiguous	-0.237	Destabilizing	0.977	D	0.457	neutral	N	0.475815742	None	None	N
K/F	0.9206	likely_pathogenic	0.8741	pathogenic	-0.241	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
K/G	0.6546	likely_pathogenic	0.5632	ambiguous	-0.672	Destabilizing	0.998	D	0.646	neutral	None	None	None	None	N
K/H	0.4143	ambiguous	0.3488	ambiguous	-1.184	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
K/I	0.6686	likely_pathogenic	0.5789	pathogenic	0.485	Stabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	N
K/L	0.6135	likely_pathogenic	0.5319	ambiguous	0.485	Stabilizing	0.995	D	0.646	neutral	None	None	None	None	N
K/M	0.4651	ambiguous	0.382	ambiguous	0.533	Stabilizing	1.0	D	0.693	prob.neutral	N	0.498327242	None	None	N
K/N	0.6484	likely_pathogenic	0.5582	ambiguous	-0.219	Destabilizing	0.993	D	0.691	prob.neutral	N	0.482029638	None	None	N
K/P	0.9426	likely_pathogenic	0.9222	pathogenic	0.24	Stabilizing	0.999	D	0.673	neutral	None	None	None	None	N
K/Q	0.2722	likely_benign	0.2266	benign	-0.384	Destabilizing	0.993	D	0.674	neutral	N	0.494748219	None	None	N
K/R	0.0834	likely_benign	0.0761	benign	-0.534	Destabilizing	0.235	N	0.271	neutral	N	0.339917234	None	None	N
K/S	0.6508	likely_pathogenic	0.5628	ambiguous	-0.762	Destabilizing	0.983	D	0.589	neutral	None	None	None	None	N
K/T	0.3585	ambiguous	0.2837	benign	-0.517	Destabilizing	0.997	D	0.685	prob.neutral	N	0.510293675	None	None	N
K/V	0.6142	likely_pathogenic	0.5218	ambiguous	0.24	Stabilizing	0.998	D	0.667	neutral	None	None	None	None	N
K/W	0.8993	likely_pathogenic	0.8528	pathogenic	-0.167	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
K/Y	0.8014	likely_pathogenic	0.7248	pathogenic	0.148	Stabilizing	0.999	D	0.684	prob.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.