TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26909	80950;80951;80952	chr2:178565407;178565406;178565405	chr2:179430134;179430133;179430132
N2AB	25268	76027;76028;76029	chr2:178565407;178565406;178565405	chr2:179430134;179430133;179430132
N2A	24341	73246;73247;73248	chr2:178565407;178565406;178565405	chr2:179430134;179430133;179430132
N2B	17844	53755;53756;53757	chr2:178565407;178565406;178565405	chr2:179430134;179430133;179430132
Novex-1	17969	54130;54131;54132	chr2:178565407;178565406;178565405	chr2:179430134;179430133;179430132
Novex-2	18036	54331;54332;54333	chr2:178565407;178565406;178565405	chr2:179430134;179430133;179430132
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-139
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.1599
• Predicted PPI site: I

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
P/L	rs1553581878	None	1.0	D	0.781	0.756	0.737821564749	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
P/L	rs1553581878	None	1.0	D	0.781	0.756	0.737821564749	gnomAD-4.0.0	6.57609E-06	None	None	None	None	I	None	2.41464E-05	0	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
P/A	0.423	ambiguous	0.4511	ambiguous	-1.623	Destabilizing	1.0	D	0.784	deleterious	D	0.537525057	None	None	I
P/C	0.9178	likely_pathogenic	0.914	pathogenic	-1.355	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	I
P/D	0.9979	likely_pathogenic	0.9977	pathogenic	-2.231	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
P/E	0.9919	likely_pathogenic	0.9911	pathogenic	-2.224	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
P/F	0.9938	likely_pathogenic	0.9935	pathogenic	-1.392	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
P/G	0.9354	likely_pathogenic	0.9351	pathogenic	-1.932	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
P/H	0.9883	likely_pathogenic	0.9874	pathogenic	-1.538	Destabilizing	1.0	D	0.7	prob.neutral	D	0.585787889	None	None	I
P/I	0.9257	likely_pathogenic	0.9294	pathogenic	-0.859	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
P/K	0.9941	likely_pathogenic	0.9939	pathogenic	-1.306	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
P/L	0.8301	likely_pathogenic	0.8261	pathogenic	-0.859	Destabilizing	1.0	D	0.781	deleterious	D	0.546484598	None	None	I
P/M	0.9542	likely_pathogenic	0.9519	pathogenic	-0.757	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
P/N	0.9944	likely_pathogenic	0.9936	pathogenic	-1.241	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
P/Q	0.9764	likely_pathogenic	0.9744	pathogenic	-1.461	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
P/R	0.984	likely_pathogenic	0.9833	pathogenic	-0.818	Destabilizing	1.0	D	0.788	deleterious	D	0.58528091	None	None	I
P/S	0.921	likely_pathogenic	0.9161	pathogenic	-1.676	Destabilizing	1.0	D	0.815	deleterious	D	0.558275885	None	None	I
P/T	0.8842	likely_pathogenic	0.8867	pathogenic	-1.568	Destabilizing	1.0	D	0.81	deleterious	D	0.573253041	None	None	I
P/V	0.8403	likely_pathogenic	0.8508	pathogenic	-1.082	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	I
P/W	0.9976	likely_pathogenic	0.9973	pathogenic	-1.621	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
P/Y	0.9956	likely_pathogenic	0.9951	pathogenic	-1.3	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I

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.