TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25045	75358;75359;75360	chr2:178570999;178570998;178570997	chr2:179435726;179435725;179435724
N2AB	23404	70435;70436;70437	chr2:178570999;178570998;178570997	chr2:179435726;179435725;179435724
N2A	22477	67654;67655;67656	chr2:178570999;178570998;178570997	chr2:179435726;179435725;179435724
N2B	15980	48163;48164;48165	chr2:178570999;178570998;178570997	chr2:179435726;179435725;179435724
Novex-1	16105	48538;48539;48540	chr2:178570999;178570998;178570997	chr2:179435726;179435725;179435724
Novex-2	16172	48739;48740;48741	chr2:178570999;178570998;178570997	chr2:179435726;179435725;179435724
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: Fn3-70
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.2711
• 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	rs1275374951	-2.182	0.981	N	0.719	0.375	0.296329037015	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
K/E	rs1275374951	-2.182	0.981	N	0.719	0.375	0.296329037015	gnomAD-4.0.0	4.1063E-06	None	None	None	None	N	None	0	6.70811E-05	None	0	0	None	0	0	1.79939E-06	0	1.65706E-05

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	0.9344	likely_pathogenic	0.9372	pathogenic	-1.505	Destabilizing	0.845	D	0.697	prob.neutral	None	None	None	None	N
K/C	0.8701	likely_pathogenic	0.8697	pathogenic	-1.655	Destabilizing	0.073	N	0.67	neutral	None	None	None	None	N
K/D	0.9919	likely_pathogenic	0.9912	pathogenic	-2.533	Highly Destabilizing	0.996	D	0.801	deleterious	None	None	None	None	N
K/E	0.8488	likely_pathogenic	0.8464	pathogenic	-2.2	Highly Destabilizing	0.981	D	0.719	prob.delet.	N	0.494094622	None	None	N
K/F	0.9684	likely_pathogenic	0.9653	pathogenic	-0.626	Destabilizing	0.987	D	0.843	deleterious	None	None	None	None	N
K/G	0.9491	likely_pathogenic	0.9475	pathogenic	-1.997	Destabilizing	0.987	D	0.78	deleterious	None	None	None	None	N
K/H	0.7504	likely_pathogenic	0.7383	pathogenic	-1.736	Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	N
K/I	0.8686	likely_pathogenic	0.8711	pathogenic	-0.079	Destabilizing	0.975	D	0.833	deleterious	None	None	None	None	N
K/L	0.799	likely_pathogenic	0.7987	pathogenic	-0.079	Destabilizing	0.845	D	0.754	deleterious	None	None	None	None	N
K/M	0.5466	ambiguous	0.5481	ambiguous	-0.511	Destabilizing	0.999	D	0.796	deleterious	N	0.483579581	None	None	N
K/N	0.959	likely_pathogenic	0.9564	pathogenic	-2.26	Highly Destabilizing	0.994	D	0.804	deleterious	N	0.505450927	None	None	N
K/P	0.9985	likely_pathogenic	0.9986	pathogenic	-0.538	Destabilizing	0.996	D	0.816	deleterious	None	None	None	None	N
K/Q	0.4283	ambiguous	0.4357	ambiguous	-1.793	Destabilizing	0.994	D	0.825	deleterious	N	0.473521605	None	None	N
K/R	0.1034	likely_benign	0.105	benign	-1.213	Destabilizing	0.981	D	0.715	prob.delet.	N	0.433766836	None	None	N
K/S	0.9475	likely_pathogenic	0.9485	pathogenic	-2.677	Highly Destabilizing	0.916	D	0.699	prob.neutral	None	None	None	None	N
K/T	0.836	likely_pathogenic	0.833	pathogenic	-2.088	Highly Destabilizing	0.967	D	0.77	deleterious	N	0.468962475	None	None	N
K/V	0.8111	likely_pathogenic	0.8151	pathogenic	-0.538	Destabilizing	0.975	D	0.779	deleterious	None	None	None	None	N
K/W	0.9392	likely_pathogenic	0.9295	pathogenic	-0.787	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
K/Y	0.861	likely_pathogenic	0.8387	pathogenic	-0.448	Destabilizing	0.996	D	0.83	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.