TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8206	24841;24842;24843	chr2:178718490;178718489;178718488	chr2:179583217;179583216;179583215
N2AB	7889	23890;23891;23892	chr2:178718490;178718489;178718488	chr2:179583217;179583216;179583215
N2A	6962	21109;21110;21111	chr2:178718490;178718489;178718488	chr2:179583217;179583216;179583215
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-67
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.2145
• 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/N	rs2154299557	None	0.993	N	0.659	0.383	0.27479166964	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
K/N	rs2154299557	None	0.993	N	0.659	0.383	0.27479166964	gnomAD-4.0.0	1.31382E-05	None	None	None	None	N	None	0	1.30804E-04	None	0	0	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	0.8905	likely_pathogenic	0.8486	pathogenic	-0.992	Destabilizing	0.983	D	0.555	neutral	None	None	None	None	N
K/C	0.9363	likely_pathogenic	0.9182	pathogenic	-0.885	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
K/D	0.9777	likely_pathogenic	0.9619	pathogenic	-0.475	Destabilizing	0.998	D	0.728	prob.delet.	None	None	None	None	N
K/E	0.7183	likely_pathogenic	0.6268	pathogenic	-0.283	Destabilizing	0.977	D	0.499	neutral	D	0.535868858	None	None	N
K/F	0.9702	likely_pathogenic	0.9605	pathogenic	-0.534	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
K/G	0.9323	likely_pathogenic	0.9045	pathogenic	-1.423	Destabilizing	0.998	D	0.694	prob.neutral	None	None	None	None	N
K/H	0.7007	likely_pathogenic	0.656	pathogenic	-1.718	Destabilizing	0.999	D	0.744	deleterious	None	None	None	None	N
K/I	0.8302	likely_pathogenic	0.7742	pathogenic	0.172	Stabilizing	0.998	D	0.805	deleterious	None	None	None	None	N
K/L	0.8294	likely_pathogenic	0.7662	pathogenic	0.172	Stabilizing	0.995	D	0.694	prob.neutral	None	None	None	None	N
K/M	0.6503	likely_pathogenic	0.5894	pathogenic	0.012	Stabilizing	1.0	D	0.74	deleterious	D	0.535615369	None	None	N
K/N	0.9259	likely_pathogenic	0.8913	pathogenic	-0.854	Destabilizing	0.993	D	0.659	neutral	N	0.517511114	None	None	N
K/P	0.9923	likely_pathogenic	0.9889	pathogenic	-0.189	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
K/Q	0.4076	ambiguous	0.3538	ambiguous	-0.763	Destabilizing	0.993	D	0.641	neutral	D	0.53510839	None	None	N
K/R	0.1177	likely_benign	0.1054	benign	-0.705	Destabilizing	0.235	N	0.325	neutral	N	0.458293143	None	None	N
K/S	0.9173	likely_pathogenic	0.8852	pathogenic	-1.549	Destabilizing	0.983	D	0.555	neutral	None	None	None	None	N
K/T	0.7838	likely_pathogenic	0.729	pathogenic	-1.117	Destabilizing	0.997	D	0.695	prob.neutral	D	0.535361879	None	None	N
K/V	0.8112	likely_pathogenic	0.7569	pathogenic	-0.189	Destabilizing	0.998	D	0.745	deleterious	None	None	None	None	N
K/W	0.9577	likely_pathogenic	0.9419	pathogenic	-0.439	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
K/Y	0.9284	likely_pathogenic	0.9005	pathogenic	-0.114	Destabilizing	0.999	D	0.78	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.