TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34281	103066;103067;103068	chr2:178533774;178533773;178533772	chr2:179398501;179398500;179398499
N2AB	32640	98143;98144;98145	chr2:178533774;178533773;178533772	chr2:179398501;179398500;179398499
N2A	31713	95362;95363;95364	chr2:178533774;178533773;178533772	chr2:179398501;179398500;179398499
N2B	25216	75871;75872;75873	chr2:178533774;178533773;178533772	chr2:179398501;179398500;179398499
Novex-1	25341	76246;76247;76248	chr2:178533774;178533773;178533772	chr2:179398501;179398500;179398499
Novex-2	25408	76447;76448;76449	chr2:178533774;178533773;178533772	chr2:179398501;179398500;179398499
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-161
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1552
• 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/L	rs758945559	-0.914	0.973	N	0.441	0.378	0.636570122401	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.85E-06	0
I/L	rs758945559	-0.914	0.973	N	0.441	0.378	0.636570122401	gnomAD-4.0.0	4.78906E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29587E-06	0	0
I/M	None	None	0.999	N	0.719	0.417	0.642701035604	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-06	0	0
I/R	rs779369864	-1.424	0.998	N	0.851	0.817	0.878042342013	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/R	rs779369864	-1.424	0.998	N	0.851	0.817	0.878042342013	gnomAD-4.0.0	1.36831E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15931E-05	1.6564E-05
I/T	rs779369864	-2.721	0.543	N	0.447	0.54	0.700574847502	gnomAD-2.1.1	3.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	7.08E-05	0
I/T	rs779369864	-2.721	0.543	N	0.447	0.54	0.700574847502	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
I/T	rs779369864	-2.721	0.543	N	0.447	0.54	0.700574847502	gnomAD-4.0.0	1.05337E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.44082E-05	0	0
I/V	rs758945559	-1.444	0.941	N	0.413	0.261	0.448794319169	gnomAD-2.1.1	8.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	8.85E-06	0
I/V	rs758945559	-1.444	0.941	N	0.413	0.261	0.448794319169	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/V	rs758945559	-1.444	0.941	N	0.413	0.261	0.448794319169	gnomAD-4.0.0	1.85885E-06	None	None	None	None	N	None	1.33451E-05	0	None	0	0	None	0	0	8.47541E-07	1.09779E-05	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
I/A	0.94	likely_pathogenic	0.9511	pathogenic	-2.454	Highly Destabilizing	0.992	D	0.715	prob.delet.	None	None	None	None	N
I/C	0.9736	likely_pathogenic	0.9824	pathogenic	-1.795	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
I/D	0.9994	likely_pathogenic	0.9993	pathogenic	-2.793	Highly Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
I/E	0.9975	likely_pathogenic	0.9974	pathogenic	-2.528	Highly Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
I/F	0.8509	likely_pathogenic	0.8918	pathogenic	-1.412	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
I/G	0.9964	likely_pathogenic	0.9972	pathogenic	-3.045	Highly Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	N
I/H	0.9982	likely_pathogenic	0.9986	pathogenic	-2.585	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
I/K	0.9947	likely_pathogenic	0.9946	pathogenic	-1.818	Destabilizing	0.998	D	0.849	deleterious	D	0.525391375	None	None	N
I/L	0.4123	ambiguous	0.4977	ambiguous	-0.729	Destabilizing	0.973	D	0.441	neutral	N	0.507030523	None	None	N
I/M	0.3797	ambiguous	0.4463	ambiguous	-0.795	Destabilizing	0.999	D	0.719	prob.delet.	N	0.513528091	None	None	N
I/N	0.9905	likely_pathogenic	0.992	pathogenic	-2.26	Highly Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
I/P	0.9979	likely_pathogenic	0.998	pathogenic	-1.286	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
I/Q	0.9957	likely_pathogenic	0.9956	pathogenic	-2.046	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
I/R	0.9928	likely_pathogenic	0.9929	pathogenic	-1.687	Destabilizing	0.998	D	0.851	deleterious	N	0.51403507	None	None	N
I/S	0.9804	likely_pathogenic	0.9846	pathogenic	-2.974	Highly Destabilizing	0.983	D	0.778	deleterious	None	None	None	None	N
I/T	0.9593	likely_pathogenic	0.9719	pathogenic	-2.546	Highly Destabilizing	0.543	D	0.447	neutral	N	0.499123116	None	None	N
I/V	0.1176	likely_benign	0.1428	benign	-1.286	Destabilizing	0.941	D	0.413	neutral	N	0.387730689	None	None	N
I/W	0.9982	likely_pathogenic	0.9989	pathogenic	-1.828	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
I/Y	0.9909	likely_pathogenic	0.9929	pathogenic	-1.51	Destabilizing	1.0	D	0.785	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.