TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25546	76861;76862;76863	chr2:178569496;178569495;178569494	chr2:179434223;179434222;179434221
N2AB	23905	71938;71939;71940	chr2:178569496;178569495;178569494	chr2:179434223;179434222;179434221
N2A	22978	69157;69158;69159	chr2:178569496;178569495;178569494	chr2:179434223;179434222;179434221
N2B	16481	49666;49667;49668	chr2:178569496;178569495;178569494	chr2:179434223;179434222;179434221
Novex-1	16606	50041;50042;50043	chr2:178569496;178569495;178569494	chr2:179434223;179434222;179434221
Novex-2	16673	50242;50243;50244	chr2:178569496;178569495;178569494	chr2:179434223;179434222;179434221
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-135
• Domain position: 33
• Structural Position: 50
• Q(SASA): 0.1846
• 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	None	None	1.0	N	0.751	0.304	0.183819452728	gnomAD-4.0.0	6.84682E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99975E-07	0	0
K/R	None	None	0.999	N	0.582	0.364	0.300784259202	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	0.9456	likely_pathogenic	0.9491	pathogenic	-1.003	Destabilizing	0.999	D	0.652	neutral	None	None	None	None	N
K/C	0.9195	likely_pathogenic	0.9264	pathogenic	-1.079	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
K/D	0.9862	likely_pathogenic	0.9886	pathogenic	-0.267	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
K/E	0.8966	likely_pathogenic	0.8991	pathogenic	-0.127	Destabilizing	0.999	D	0.555	neutral	D	0.525500058	None	None	N
K/F	0.9557	likely_pathogenic	0.9492	pathogenic	-0.756	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
K/G	0.9652	likely_pathogenic	0.9697	pathogenic	-1.375	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
K/H	0.7371	likely_pathogenic	0.7465	pathogenic	-1.701	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
K/I	0.7903	likely_pathogenic	0.7614	pathogenic	-0.025	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
K/L	0.7671	likely_pathogenic	0.7638	pathogenic	-0.025	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
K/M	0.6646	likely_pathogenic	0.6525	pathogenic	-0.105	Destabilizing	1.0	D	0.751	deleterious	N	0.502533957	None	None	N
K/N	0.9526	likely_pathogenic	0.9545	pathogenic	-0.709	Destabilizing	1.0	D	0.751	deleterious	N	0.507306897	None	None	N
K/P	0.9869	likely_pathogenic	0.9892	pathogenic	-0.323	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
K/Q	0.6226	likely_pathogenic	0.6216	pathogenic	-0.789	Destabilizing	1.0	D	0.741	deleterious	N	0.498241543	None	None	N
K/R	0.0947	likely_benign	0.0965	benign	-0.7	Destabilizing	0.999	D	0.582	neutral	N	0.458848921	None	None	N
K/S	0.972	likely_pathogenic	0.9748	pathogenic	-1.493	Destabilizing	0.999	D	0.608	neutral	None	None	None	None	N
K/T	0.8794	likely_pathogenic	0.8764	pathogenic	-1.132	Destabilizing	1.0	D	0.783	deleterious	D	0.524993079	None	None	N
K/V	0.783	likely_pathogenic	0.7779	pathogenic	-0.323	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
K/W	0.9549	likely_pathogenic	0.9526	pathogenic	-0.564	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
K/Y	0.914	likely_pathogenic	0.9105	pathogenic	-0.246	Destabilizing	1.0	D	0.81	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.