TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25734	77425;77426;77427	chr2:178568932;178568931;178568930	chr2:179433659;179433658;179433657
N2AB	24093	72502;72503;72504	chr2:178568932;178568931;178568930	chr2:179433659;179433658;179433657
N2A	23166	69721;69722;69723	chr2:178568932;178568931;178568930	chr2:179433659;179433658;179433657
N2B	16669	50230;50231;50232	chr2:178568932;178568931;178568930	chr2:179433659;179433658;179433657
Novex-1	16794	50605;50606;50607	chr2:178568932;178568931;178568930	chr2:179433659;179433658;179433657
Novex-2	16861	50806;50807;50808	chr2:178568932;178568931;178568930	chr2:179433659;179433658;179433657
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-75
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.1861
• 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
I/V	None	None	0.002	N	0.192	0.052	0.408853032482	gnomAD-4.0.0	2.73739E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69874E-06	0	1.65689E-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
I/A	0.2712	likely_benign	0.2338	benign	-2.99	Highly Destabilizing	0.891	D	0.649	neutral	None	None	None	None	N
I/C	0.6558	likely_pathogenic	0.6122	pathogenic	-2.247	Highly Destabilizing	1.0	D	0.625	neutral	None	None	None	None	N
I/D	0.7432	likely_pathogenic	0.6349	pathogenic	-3.447	Highly Destabilizing	0.952	D	0.718	prob.delet.	None	None	None	None	N
I/E	0.5993	likely_pathogenic	0.5411	ambiguous	-3.256	Highly Destabilizing	0.142	N	0.593	neutral	None	None	None	None	N
I/F	0.1942	likely_benign	0.1616	benign	-1.764	Destabilizing	0.977	D	0.692	prob.neutral	N	0.518441516	None	None	N
I/G	0.7379	likely_pathogenic	0.6734	pathogenic	-3.471	Highly Destabilizing	0.988	D	0.737	prob.delet.	None	None	None	None	N
I/H	0.4756	ambiguous	0.4017	ambiguous	-2.739	Highly Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
I/K	0.4927	ambiguous	0.4294	ambiguous	-2.458	Highly Destabilizing	0.538	D	0.713	prob.delet.	None	None	None	None	N
I/L	0.1283	likely_benign	0.1081	benign	-1.591	Destabilizing	0.074	N	0.427	neutral	N	0.482019356	None	None	N
I/M	0.1105	likely_benign	0.0993	benign	-1.573	Destabilizing	0.962	D	0.656	neutral	N	0.494081395	None	None	N
I/N	0.3563	ambiguous	0.2633	benign	-2.72	Highly Destabilizing	0.995	D	0.724	prob.delet.	N	0.465048454	None	None	N
I/P	0.9843	likely_pathogenic	0.9746	pathogenic	-2.042	Highly Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
I/Q	0.5012	ambiguous	0.4454	ambiguous	-2.658	Highly Destabilizing	0.983	D	0.729	prob.delet.	None	None	None	None	N
I/R	0.3828	ambiguous	0.3256	benign	-1.951	Destabilizing	0.982	D	0.715	prob.delet.	None	None	None	None	N
I/S	0.2851	likely_benign	0.2391	benign	-3.341	Highly Destabilizing	0.968	D	0.681	prob.neutral	N	0.463287254	None	None	N
I/T	0.122	likely_benign	0.1165	benign	-3.033	Highly Destabilizing	0.9	D	0.684	prob.neutral	N	0.498911606	None	None	N
I/V	0.0735	likely_benign	0.0706	benign	-2.042	Highly Destabilizing	0.002	N	0.192	neutral	N	0.438999298	None	None	N
I/W	0.7719	likely_pathogenic	0.7166	pathogenic	-2.114	Highly Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
I/Y	0.5498	ambiguous	0.4722	ambiguous	-1.945	Destabilizing	0.929	D	0.688	prob.neutral	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.