TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34395	103408;103409;103410	chr2:178533432;178533431;178533430	chr2:179398159;179398158;179398157
N2AB	32754	98485;98486;98487	chr2:178533432;178533431;178533430	chr2:179398159;179398158;179398157
N2A	31827	95704;95705;95706	chr2:178533432;178533431;178533430	chr2:179398159;179398158;179398157
N2B	25330	76213;76214;76215	chr2:178533432;178533431;178533430	chr2:179398159;179398158;179398157
Novex-1	25455	76588;76589;76590	chr2:178533432;178533431;178533430	chr2:179398159;179398158;179398157
Novex-2	25522	76789;76790;76791	chr2:178533432;178533431;178533430	chr2:179398159;179398158;179398157
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-162
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.6794
• 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/Q	rs368320079	0.021	0.968	N	0.646	0.238	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
K/Q	rs368320079	0.021	0.968	N	0.646	0.238	None	gnomAD-4.0.0	3.18218E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.7154E-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	0.5911	likely_pathogenic	0.5658	pathogenic	-0.206	Destabilizing	0.851	D	0.609	neutral	None	None	None	None	I
K/C	0.771	likely_pathogenic	0.7374	pathogenic	-0.225	Destabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	I
K/D	0.8969	likely_pathogenic	0.866	pathogenic	0.148	Stabilizing	0.851	D	0.621	neutral	None	None	None	None	I
K/E	0.3871	ambiguous	0.326	benign	0.207	Stabilizing	0.103	N	0.389	neutral	N	0.489343265	None	None	I
K/F	0.8841	likely_pathogenic	0.8501	pathogenic	-0.107	Destabilizing	0.988	D	0.716	prob.delet.	None	None	None	None	I
K/G	0.853	likely_pathogenic	0.8332	pathogenic	-0.509	Destabilizing	0.919	D	0.636	neutral	None	None	None	None	I
K/H	0.3602	ambiguous	0.3196	benign	-0.889	Destabilizing	0.076	N	0.455	neutral	None	None	None	None	I
K/I	0.4102	ambiguous	0.3463	ambiguous	0.542	Stabilizing	0.968	D	0.709	prob.delet.	N	0.498216252	None	None	I
K/L	0.4395	ambiguous	0.4263	ambiguous	0.542	Stabilizing	0.851	D	0.646	neutral	None	None	None	None	I
K/M	0.3297	likely_benign	0.3039	benign	0.394	Stabilizing	0.999	D	0.658	neutral	None	None	None	None	I
K/N	0.6962	likely_pathogenic	0.631	pathogenic	0.07	Stabilizing	0.896	D	0.601	neutral	N	0.484580374	None	None	I
K/P	0.9939	likely_pathogenic	0.9907	pathogenic	0.324	Stabilizing	0.988	D	0.67	neutral	None	None	None	None	I
K/Q	0.156	likely_benign	0.143	benign	-0.071	Destabilizing	0.968	D	0.646	neutral	N	0.494405156	None	None	I
K/R	0.104	likely_benign	0.0988	benign	-0.278	Destabilizing	0.896	D	0.602	neutral	N	0.482092006	None	None	I
K/S	0.6603	likely_pathogenic	0.617	pathogenic	-0.528	Destabilizing	0.851	D	0.611	neutral	None	None	None	None	I
K/T	0.2261	likely_benign	0.2031	benign	-0.285	Destabilizing	0.103	N	0.389	neutral	N	0.426198651	None	None	I
K/V	0.4154	ambiguous	0.3684	ambiguous	0.324	Stabilizing	0.851	D	0.65	neutral	None	None	None	None	I
K/W	0.8996	likely_pathogenic	0.8676	pathogenic	-0.022	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	I
K/Y	0.7968	likely_pathogenic	0.7527	pathogenic	0.289	Stabilizing	0.976	D	0.694	prob.neutral	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.