TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9777	29554;29555;29556	chr2:178706545;178706544;178706543	chr2:179571272;179571271;179571270
N2AB	9460	28603;28604;28605	chr2:178706545;178706544;178706543	chr2:179571272;179571271;179571270
N2A	8533	25822;25823;25824	chr2:178706545;178706544;178706543	chr2:179571272;179571271;179571270
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: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-83
• Domain position: 80
• Structural Position: 163
• Q(SASA): 0.9714
• 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
H/R	rs776520121	0.188	1.0	None	0.667	0.45	0.326616659874	gnomAD-2.1.1	4.01E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.85E-06	0
H/R	rs776520121	0.188	1.0	None	0.667	0.45	0.326616659874	gnomAD-4.0.0	6.1577E-06	None	None	None	None	I	None	2.98757E-05	0	None	0	0	None	0	0	6.2962E-06	0	1.65634E-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
H/A	0.6456	likely_pathogenic	0.5329	ambiguous	0.393	Stabilizing	0.999	D	0.591	neutral	None	None	None	None	I
H/C	0.5303	ambiguous	0.4306	ambiguous	0.623	Stabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
H/D	0.5939	likely_pathogenic	0.5176	ambiguous	-0.134	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	I
H/E	0.6815	likely_pathogenic	0.6006	pathogenic	-0.129	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	I
H/F	0.3907	ambiguous	0.3694	ambiguous	0.909	Stabilizing	1.0	D	0.653	neutral	None	None	None	None	I
H/G	0.7495	likely_pathogenic	0.6537	pathogenic	0.16	Stabilizing	0.999	D	0.589	neutral	None	None	None	None	I
H/I	0.735	likely_pathogenic	0.6582	pathogenic	0.967	Stabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	I
H/K	0.397	ambiguous	0.3878	ambiguous	0.296	Stabilizing	1.0	D	0.618	neutral	None	None	None	None	I
H/L	0.3882	ambiguous	0.3106	benign	0.967	Stabilizing	1.0	D	0.657	neutral	None	None	None	None	I
H/M	0.7839	likely_pathogenic	0.731	pathogenic	0.682	Stabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
H/N	0.2452	likely_benign	0.2192	benign	0.23	Stabilizing	0.999	D	0.644	neutral	None	None	None	None	I
H/P	0.9428	likely_pathogenic	0.879	pathogenic	0.8	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	I
H/Q	0.4336	ambiguous	0.3699	ambiguous	0.291	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
H/R	0.2243	likely_benign	0.1912	benign	-0.195	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
H/S	0.6161	likely_pathogenic	0.5157	ambiguous	0.347	Stabilizing	1.0	D	0.613	neutral	None	None	None	None	I
H/T	0.7002	likely_pathogenic	0.6307	pathogenic	0.445	Stabilizing	1.0	D	0.662	neutral	None	None	None	None	I
H/V	0.6684	likely_pathogenic	0.5828	pathogenic	0.8	Stabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	I
H/W	0.6791	likely_pathogenic	0.5928	pathogenic	0.815	Stabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
H/Y	0.1633	likely_benign	0.1344	benign	1.1	Stabilizing	0.999	D	0.581	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.