TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7940	24043;24044;24045	chr2:178719674;178719673;178719672	chr2:179584401;179584400;179584399
N2AB	7623	23092;23093;23094	chr2:178719674;178719673;178719672	chr2:179584401;179584400;179584399
N2A	6696	20311;20312;20313	chr2:178719674;178719673;178719672	chr2:179584401;179584400;179584399
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-64
• Domain position: 52
• Structural Position: 130
• Q(SASA): 0.4508
• 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/N	None	None	0.033	N	0.427	0.131	0.461058313273	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
I/V	None	None	None	N	0.079	0.129	0.159798565429	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
I/A	0.1432	likely_benign	0.1818	benign	-0.61	Destabilizing	None	N	0.125	neutral	None	None	None	None	N
I/C	0.3898	ambiguous	0.4289	ambiguous	-0.681	Destabilizing	0.245	N	0.261	neutral	None	None	None	None	N
I/D	0.3164	likely_benign	0.3512	ambiguous	0.055	Stabilizing	0.009	N	0.353	neutral	None	None	None	None	N
I/E	0.2486	likely_benign	0.2682	benign	-0.012	Destabilizing	None	N	0.198	neutral	None	None	None	None	N
I/F	0.0757	likely_benign	0.0839	benign	-0.51	Destabilizing	None	N	0.072	neutral	N	0.422139625	None	None	N
I/G	0.285	likely_benign	0.352	ambiguous	-0.785	Destabilizing	0.009	N	0.325	neutral	None	None	None	None	N
I/H	0.1805	likely_benign	0.1863	benign	None	Stabilizing	0.497	N	0.389	neutral	None	None	None	None	N
I/K	0.154	likely_benign	0.152	benign	-0.318	Destabilizing	None	N	0.196	neutral	None	None	None	None	N
I/L	0.0693	likely_benign	0.0771	benign	-0.266	Destabilizing	None	N	0.074	neutral	N	0.434183416	None	None	N
I/M	0.0706	likely_benign	0.0793	benign	-0.45	Destabilizing	0.108	N	0.24	neutral	N	0.497290745	None	None	N
I/N	0.1062	likely_benign	0.1169	benign	-0.198	Destabilizing	0.033	N	0.427	neutral	N	0.459463076	None	None	N
I/P	0.5773	likely_pathogenic	0.6256	pathogenic	-0.348	Destabilizing	None	N	0.208	neutral	None	None	None	None	N
I/Q	0.1507	likely_benign	0.1609	benign	-0.355	Destabilizing	0.044	N	0.459	neutral	None	None	None	None	N
I/R	0.1052	likely_benign	0.1048	benign	0.175	Stabilizing	0.022	N	0.429	neutral	None	None	None	None	N
I/S	0.1075	likely_benign	0.1204	benign	-0.688	Destabilizing	None	N	0.144	neutral	N	0.409188971	None	None	N
I/T	0.0997	likely_benign	0.1228	benign	-0.642	Destabilizing	None	N	0.124	neutral	N	0.413325354	None	None	N
I/V	0.0679	likely_benign	0.0751	benign	-0.348	Destabilizing	None	N	0.079	neutral	N	0.415885657	None	None	N
I/W	0.3919	ambiguous	0.4456	ambiguous	-0.536	Destabilizing	0.788	D	0.362	neutral	None	None	None	None	N
I/Y	0.2329	likely_benign	0.2416	benign	-0.296	Destabilizing	0.022	N	0.362	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.