TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19698	59317;59318;59319	chr2:178593027;178593026;178593025	chr2:179457754;179457753;179457752
N2AB	18057	54394;54395;54396	chr2:178593027;178593026;178593025	chr2:179457754;179457753;179457752
N2A	17130	51613;51614;51615	chr2:178593027;178593026;178593025	chr2:179457754;179457753;179457752
N2B	10633	32122;32123;32124	chr2:178593027;178593026;178593025	chr2:179457754;179457753;179457752
Novex-1	10758	32497;32498;32499	chr2:178593027;178593026;178593025	chr2:179457754;179457753;179457752
Novex-2	10825	32698;32699;32700	chr2:178593027;178593026;178593025	chr2:179457754;179457753;179457752
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-31
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.1858
• 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
D/A	rs878974246	None	0.027	N	0.617	0.224	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
D/A	rs878974246	None	0.027	N	0.617	0.224	None	gnomAD-4.0.0	4.9587E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.78187E-06	0	0
D/H	rs397517642	-1.061	0.705	N	0.665	0.284	0.264081493735	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.66003E-04
D/H	rs397517642	-1.061	0.705	N	0.665	0.284	0.264081493735	gnomAD-4.0.0	6.84343E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65673E-05
D/N	None	-0.858	0.426	N	0.607	0.254	0.21279746466	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	2.9E-05	None	0	5.6E-05	None	0	None	0	8.91E-06	0
D/N	None	-0.858	0.426	N	0.607	0.254	0.21279746466	gnomAD-4.0.0	6.84343E-06	None	None	None	None	N	None	2.98954E-05	2.23784E-05	None	0	5.04974E-05	None	0	0	4.49788E-06	1.15958E-05	0
D/Y	rs397517642	-0.621	0.879	N	0.72	0.302	0.298403945805	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	8.91E-06	0
D/Y	rs397517642	-0.621	0.879	N	0.72	0.302	0.298403945805	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	4.78469E-04
D/Y	rs397517642	-0.621	0.879	N	0.72	0.302	0.298403945805	gnomAD-4.0.0	9.29797E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.6296E-06	4.3928E-05	3.20256E-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
D/A	0.2965	likely_benign	0.2308	benign	-0.393	Destabilizing	0.027	N	0.617	neutral	N	0.42697415	None	None	N
D/C	0.6919	likely_pathogenic	0.606	pathogenic	-0.195	Destabilizing	0.935	D	0.706	prob.neutral	None	None	None	None	N
D/E	0.2694	likely_benign	0.2052	benign	-0.859	Destabilizing	None	N	0.233	neutral	N	0.414967645	None	None	N
D/F	0.5541	ambiguous	0.5137	ambiguous	-0.483	Destabilizing	0.791	D	0.717	prob.delet.	None	None	None	None	N
D/G	0.4619	ambiguous	0.3532	ambiguous	-0.718	Destabilizing	0.117	N	0.623	neutral	N	0.466089899	None	None	N
D/H	0.3702	ambiguous	0.3265	benign	-0.909	Destabilizing	0.705	D	0.665	neutral	N	0.465396465	None	None	N
D/I	0.3807	ambiguous	0.3123	benign	0.451	Stabilizing	0.38	N	0.721	prob.delet.	None	None	None	None	N
D/K	0.6749	likely_pathogenic	0.5837	pathogenic	-0.444	Destabilizing	0.081	N	0.635	neutral	None	None	None	None	N
D/L	0.4106	ambiguous	0.3581	ambiguous	0.451	Stabilizing	0.149	N	0.698	prob.neutral	None	None	None	None	N
D/M	0.6003	likely_pathogenic	0.5377	ambiguous	0.91	Stabilizing	0.935	D	0.708	prob.delet.	None	None	None	None	N
D/N	0.1558	likely_benign	0.119	benign	-0.703	Destabilizing	0.426	N	0.607	neutral	N	0.415295719	None	None	N
D/P	0.9582	likely_pathogenic	0.9436	pathogenic	0.195	Stabilizing	0.555	D	0.715	prob.delet.	None	None	None	None	N
D/Q	0.5182	ambiguous	0.4313	ambiguous	-0.593	Destabilizing	0.235	N	0.662	neutral	None	None	None	None	N
D/R	0.6903	likely_pathogenic	0.6185	pathogenic	-0.467	Destabilizing	0.235	N	0.697	prob.neutral	None	None	None	None	N
D/S	0.1613	likely_benign	0.1304	benign	-1.001	Destabilizing	0.007	N	0.286	neutral	None	None	None	None	N
D/T	0.2445	likely_benign	0.2063	benign	-0.736	Destabilizing	0.001	N	0.375	neutral	None	None	None	None	N
D/V	0.2658	likely_benign	0.2115	benign	0.195	Stabilizing	0.117	N	0.691	prob.neutral	N	0.385087455	None	None	N
D/W	0.8831	likely_pathogenic	0.8714	pathogenic	-0.517	Destabilizing	0.935	D	0.725	prob.delet.	None	None	None	None	N
D/Y	0.2523	likely_benign	0.2099	benign	-0.287	Destabilizing	0.879	D	0.72	prob.delet.	N	0.449216292	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.