TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32393	97402;97403;97404	chr2:178542677;178542676;178542675	chr2:179407404;179407403;179407402
N2AB	30752	92479;92480;92481	chr2:178542677;178542676;178542675	chr2:179407404;179407403;179407402
N2A	29825	89698;89699;89700	chr2:178542677;178542676;178542675	chr2:179407404;179407403;179407402
N2B	23328	70207;70208;70209	chr2:178542677;178542676;178542675	chr2:179407404;179407403;179407402
Novex-1	23453	70582;70583;70584	chr2:178542677;178542676;178542675	chr2:179407404;179407403;179407402
Novex-2	23520	70783;70784;70785	chr2:178542677;178542676;178542675	chr2:179407404;179407403;179407402
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-154
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.4231
• 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
K/E	rs374081110	0.013	0.201	N	0.555	0.232	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	5.56E-05	None	0	None	0	0	0
K/E	rs374081110	0.013	0.201	N	0.555	0.232	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/E	rs374081110	0.013	0.201	N	0.555	0.232	None	gnomAD-4.0.0	2.47967E-06	None	None	None	None	I	None	1.33494E-05	0	None	0	2.22866E-05	None	0	0	1.69597E-06	0	0
K/R	None	None	0.002	D	0.359	0.141	0.315609569513	gnomAD-4.0.0	1.59291E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86274E-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	0.447	ambiguous	0.4417	ambiguous	-0.63	Destabilizing	0.399	N	0.63	neutral	None	None	None	None	I
K/C	0.7024	likely_pathogenic	0.6897	pathogenic	-0.8	Destabilizing	0.982	D	0.694	prob.neutral	None	None	None	None	I
K/D	0.6334	likely_pathogenic	0.6478	pathogenic	-0.278	Destabilizing	0.539	D	0.705	prob.neutral	None	None	None	None	I
K/E	0.2547	likely_benign	0.2562	benign	-0.15	Destabilizing	0.201	N	0.555	neutral	N	0.471045506	None	None	I
K/F	0.8412	likely_pathogenic	0.8411	pathogenic	-0.239	Destabilizing	0.982	D	0.739	prob.delet.	None	None	None	None	I
K/G	0.6019	likely_pathogenic	0.5731	pathogenic	-1.014	Destabilizing	0.25	N	0.688	prob.neutral	None	None	None	None	I
K/H	0.2477	likely_benign	0.2416	benign	-1.324	Destabilizing	0.7	D	0.715	prob.delet.	None	None	None	None	I
K/I	0.507	ambiguous	0.516	ambiguous	0.373	Stabilizing	0.781	D	0.751	deleterious	N	0.517879448	None	None	I
K/L	0.4927	ambiguous	0.4872	ambiguous	0.373	Stabilizing	0.7	D	0.706	prob.neutral	None	None	None	None	I
K/M	0.3087	likely_benign	0.3042	benign	0.16	Stabilizing	0.982	D	0.689	prob.neutral	None	None	None	None	I
K/N	0.411	ambiguous	0.4273	ambiguous	-0.664	Destabilizing	0.004	N	0.341	neutral	N	0.475358035	None	None	I
K/P	0.8949	likely_pathogenic	0.8823	pathogenic	0.069	Stabilizing	0.826	D	0.743	deleterious	None	None	None	None	I
K/Q	0.1475	likely_benign	0.1443	benign	-0.712	Destabilizing	0.638	D	0.633	neutral	N	0.512625557	None	None	I
K/R	0.0869	likely_benign	0.0841	benign	-0.716	Destabilizing	0.002	N	0.359	neutral	D	0.528056369	None	None	I
K/S	0.4269	ambiguous	0.4269	ambiguous	-1.324	Destabilizing	0.25	N	0.559	neutral	None	None	None	None	I
K/T	0.1696	likely_benign	0.1733	benign	-0.985	Destabilizing	0.201	N	0.687	prob.neutral	N	0.448728794	None	None	I
K/V	0.4625	ambiguous	0.4697	ambiguous	0.069	Stabilizing	0.826	D	0.752	deleterious	None	None	None	None	I
K/W	0.7828	likely_pathogenic	0.7594	pathogenic	-0.112	Destabilizing	0.982	D	0.633	neutral	None	None	None	None	I
K/Y	0.6932	likely_pathogenic	0.6832	pathogenic	0.189	Stabilizing	0.935	D	0.751	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.