TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5087	15484;15485;15486	chr2:178734565;178734564;178734563	chr2:179599292;179599291;179599290
N2AB	4770	14533;14534;14535	chr2:178734565;178734564;178734563	chr2:179599292;179599291;179599290
N2A	3843	11752;11753;11754	chr2:178734565;178734564;178734563	chr2:179599292;179599291;179599290
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: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-34
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.5439
• 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
V/M	rs751652571	-0.435	0.999	N	0.583	0.177	0.577502390439	gnomAD-2.1.1	1.5E-05	None	None	None	None	I	None	4.21E-05	0	None	0	0	None	1.12124E-04	None	0	0	0
V/M	rs751652571	-0.435	0.999	N	0.583	0.177	0.577502390439	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/M	rs751652571	-0.435	0.999	N	0.583	0.177	0.577502390439	gnomAD-4.0.0	4.38724E-06	None	None	None	None	I	None	1.34448E-05	0	None	0	0	None	0	0	0	6.84041E-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
V/A	0.5302	ambiguous	0.2895	benign	-0.417	Destabilizing	0.998	D	0.525	neutral	N	0.505910225	None	None	I
V/C	0.9387	likely_pathogenic	0.8702	pathogenic	-0.889	Destabilizing	1.0	D	0.594	neutral	None	None	None	None	I
V/D	0.883	likely_pathogenic	0.6021	pathogenic	-0.033	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	I
V/E	0.7297	likely_pathogenic	0.4387	ambiguous	-0.127	Destabilizing	1.0	D	0.659	neutral	N	0.502497972	None	None	I
V/F	0.4668	ambiguous	0.2593	benign	-0.605	Destabilizing	0.999	D	0.589	neutral	None	None	None	None	I
V/G	0.6359	likely_pathogenic	0.3371	benign	-0.51	Destabilizing	1.0	D	0.695	prob.neutral	D	0.570265623	None	None	I
V/H	0.9258	likely_pathogenic	0.7711	pathogenic	-0.005	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
V/I	0.0931	likely_benign	0.0822	benign	-0.31	Destabilizing	0.985	D	0.471	neutral	None	None	None	None	I
V/K	0.792	likely_pathogenic	0.5268	ambiguous	-0.408	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	I
V/L	0.3329	likely_benign	0.2044	benign	-0.31	Destabilizing	0.434	N	0.324	neutral	N	0.442817875	None	None	I
V/M	0.344	ambiguous	0.1937	benign	-0.591	Destabilizing	0.999	D	0.583	neutral	N	0.508497722	None	None	I
V/N	0.7699	likely_pathogenic	0.4618	ambiguous	-0.314	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	I
V/P	0.7387	likely_pathogenic	0.5295	ambiguous	-0.316	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	I
V/Q	0.7134	likely_pathogenic	0.4548	ambiguous	-0.459	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	I
V/R	0.7572	likely_pathogenic	0.4971	ambiguous	0.003	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
V/S	0.6102	likely_pathogenic	0.3269	benign	-0.691	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	I
V/T	0.4528	ambiguous	0.2417	benign	-0.681	Destabilizing	0.998	D	0.567	neutral	None	None	None	None	I
V/W	0.9692	likely_pathogenic	0.9073	pathogenic	-0.67	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
V/Y	0.9039	likely_pathogenic	0.7566	pathogenic	-0.408	Destabilizing	1.0	D	0.592	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.