TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9268	28027;28028;28029	chr2:178712028;178712027;178712026	chr2:179576755;179576754;179576753
N2AB	8951	27076;27077;27078	chr2:178712028;178712027;178712026	chr2:179576755;179576754;179576753
N2A	8024	24295;24296;24297	chr2:178712028;178712027;178712026	chr2:179576755;179576754;179576753
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-78
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.3422
• 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
D/N	rs751988610	-0.127	0.549	N	0.22	0.17	0.227934060464	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	5.56E-05	None	0	None	0	0	0
D/N	rs751988610	-0.127	0.549	N	0.22	0.17	0.227934060464	gnomAD-4.0.0	1.59139E-06	None	None	None	None	I	None	0	0	None	0	2.77254E-05	None	0	0	0	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
D/A	0.138	likely_benign	0.2276	benign	-0.408	Destabilizing	0.016	N	0.255	neutral	N	0.47987842	None	None	I
D/C	0.5676	likely_pathogenic	0.7506	pathogenic	-0.041	Destabilizing	0.992	D	0.378	neutral	None	None	None	None	I
D/E	0.1764	likely_benign	0.2329	benign	-0.458	Destabilizing	0.712	D	0.219	neutral	N	0.47976099	None	None	I
D/F	0.5061	ambiguous	0.6612	pathogenic	-0.209	Destabilizing	0.972	D	0.376	neutral	None	None	None	None	I
D/G	0.1276	likely_benign	0.2092	benign	-0.669	Destabilizing	0.002	N	0.19	neutral	N	0.496637384	None	None	I
D/H	0.2194	likely_benign	0.3221	benign	-0.25	Destabilizing	0.99	D	0.329	neutral	N	0.493751795	None	None	I
D/I	0.3578	ambiguous	0.5153	ambiguous	0.252	Stabilizing	0.85	D	0.381	neutral	None	None	None	None	I
D/K	0.3204	likely_benign	0.4188	ambiguous	0.073	Stabilizing	0.617	D	0.323	neutral	None	None	None	None	I
D/L	0.3195	likely_benign	0.4556	ambiguous	0.252	Stabilizing	0.617	D	0.353	neutral	None	None	None	None	I
D/M	0.5111	ambiguous	0.6732	pathogenic	0.502	Stabilizing	0.992	D	0.371	neutral	None	None	None	None	I
D/N	0.074	likely_benign	0.0995	benign	-0.313	Destabilizing	0.549	D	0.22	neutral	N	0.466141119	None	None	I
D/P	0.8169	likely_pathogenic	0.9273	pathogenic	0.056	Stabilizing	0.92	D	0.304	neutral	None	None	None	None	I
D/Q	0.286	likely_benign	0.3855	ambiguous	-0.241	Destabilizing	0.972	D	0.316	neutral	None	None	None	None	I
D/R	0.3311	likely_benign	0.4609	ambiguous	0.252	Stabilizing	0.92	D	0.349	neutral	None	None	None	None	I
D/S	0.0983	likely_benign	0.1375	benign	-0.451	Destabilizing	0.25	N	0.225	neutral	None	None	None	None	I
D/T	0.188	likely_benign	0.2903	benign	-0.245	Destabilizing	0.009	N	0.213	neutral	None	None	None	None	I
D/V	0.2227	likely_benign	0.3294	benign	0.056	Stabilizing	0.549	D	0.335	neutral	N	0.495367948	None	None	I
D/W	0.8596	likely_pathogenic	0.9341	pathogenic	-0.043	Destabilizing	0.992	D	0.447	neutral	None	None	None	None	I
D/Y	0.2225	likely_benign	0.333	benign	0.032	Stabilizing	0.963	D	0.375	neutral	D	0.526786933	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.