TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25192	75799;75800;75801	chr2:178570558;178570557;178570556	chr2:179435285;179435284;179435283
N2AB	23551	70876;70877;70878	chr2:178570558;178570557;178570556	chr2:179435285;179435284;179435283
N2A	22624	68095;68096;68097	chr2:178570558;178570557;178570556	chr2:179435285;179435284;179435283
N2B	16127	48604;48605;48606	chr2:178570558;178570557;178570556	chr2:179435285;179435284;179435283
Novex-1	16252	48979;48980;48981	chr2:178570558;178570557;178570556	chr2:179435285;179435284;179435283
Novex-2	16319	49180;49181;49182	chr2:178570558;178570557;178570556	chr2:179435285;179435284;179435283
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-134
• Domain position: 82
• Structural Position: 165
• Q(SASA): 0.4976
• 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
E/A	None	-0.644	0.999	N	0.71	0.625	0.557519804684	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/A	None	-0.644	0.999	N	0.71	0.625	0.557519804684	gnomAD-4.0.0	6.84394E-07	None	None	None	None	I	None	0	2.23784E-05	None	0	0	None	0	0	0	0	0
E/G	rs998111823	None	1.0	D	0.673	0.632	0.617623114376	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
E/G	rs998111823	None	1.0	D	0.673	0.632	0.617623114376	gnomAD-4.0.0	2.47949E-06	None	None	None	None	I	None	5.3416E-05	0	None	0	0	None	0	0	0	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
E/A	0.167	likely_benign	0.1912	benign	-0.404	Destabilizing	0.999	D	0.71	prob.delet.	N	0.505041714	None	None	I
E/C	0.7841	likely_pathogenic	0.8237	pathogenic	-0.067	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
E/D	0.1657	likely_benign	0.1676	benign	-0.374	Destabilizing	0.999	D	0.495	neutral	N	0.505802182	None	None	I
E/F	0.6712	likely_pathogenic	0.6972	pathogenic	-0.253	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
E/G	0.1981	likely_benign	0.2217	benign	-0.6	Destabilizing	1.0	D	0.673	neutral	D	0.524666906	None	None	I
E/H	0.4604	ambiguous	0.5014	ambiguous	0.003	Stabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
E/I	0.304	likely_benign	0.3381	benign	0.078	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
E/K	0.1907	likely_benign	0.2205	benign	0.368	Stabilizing	0.999	D	0.693	prob.neutral	N	0.518050019	None	None	I
E/L	0.4124	ambiguous	0.4489	ambiguous	0.078	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
E/M	0.3978	ambiguous	0.428	ambiguous	0.158	Stabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
E/N	0.283	likely_benign	0.2982	benign	-0.013	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	I
E/P	0.9022	likely_pathogenic	0.9234	pathogenic	-0.063	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
E/Q	0.135	likely_benign	0.1515	benign	0.021	Stabilizing	1.0	D	0.635	neutral	D	0.532520826	None	None	I
E/R	0.3314	likely_benign	0.3827	ambiguous	0.57	Stabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	I
E/S	0.1534	likely_benign	0.167	benign	-0.157	Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	I
E/T	0.1579	likely_benign	0.1784	benign	0.007	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
E/V	0.1863	likely_benign	0.2084	benign	-0.063	Destabilizing	1.0	D	0.733	prob.delet.	N	0.493889672	None	None	I
E/W	0.8653	likely_pathogenic	0.8894	pathogenic	-0.082	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
E/Y	0.5736	likely_pathogenic	0.6229	pathogenic	None	Stabilizing	1.0	D	0.707	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.