TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7525	22798;22799;22800	chr2:178722090;178722089;178722088	chr2:179586817;179586816;179586815
N2AB	7208	21847;21848;21849	chr2:178722090;178722089;178722088	chr2:179586817;179586816;179586815
N2A	6281	19066;19067;19068	chr2:178722090;178722089;178722088	chr2:179586817;179586816;179586815
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-60
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.63
• 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/E	rs200061856	0.148	0.003	N	0.123	0.079	0.220303561663	gnomAD-2.1.1	6.58E-05	None	None	None	None	N	None	0	2.94E-05	None	0	0	None	6.91E-05	None	0	1.17749E-04	0
D/E	rs200061856	0.148	0.003	N	0.123	0.079	0.220303561663	gnomAD-3.1.2	4.6E-05	None	None	None	None	N	None	0	0	1.09649E-03	0	0	None	0	0	8.82E-05	0	0
D/E	rs200061856	0.148	0.003	N	0.123	0.079	0.220303561663	gnomAD-4.0.0	3.29919E-05	None	None	None	None	N	None	0	1.67904E-05	None	0	0	None	0	0	3.91229E-05	2.23324E-05	4.82765E-05
D/H	None	None	0.995	N	0.523	0.345	0.463586170655	gnomAD-4.0.0	2.06407E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.70908E-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
D/A	0.1945	likely_benign	0.1939	benign	-0.283	Destabilizing	0.475	N	0.493	neutral	N	0.416520375	None	None	N
D/C	0.7616	likely_pathogenic	0.7375	pathogenic	-0.031	Destabilizing	0.983	D	0.703	prob.neutral	None	None	None	None	N
D/E	0.1608	likely_benign	0.1771	benign	-0.311	Destabilizing	0.003	N	0.123	neutral	N	0.373844246	None	None	N
D/F	0.6871	likely_pathogenic	0.6759	pathogenic	-0.06	Destabilizing	0.995	D	0.636	neutral	None	None	None	None	N
D/G	0.2305	likely_benign	0.2065	benign	-0.51	Destabilizing	0.002	N	0.239	neutral	N	0.456964275	None	None	N
D/H	0.3317	likely_benign	0.3342	benign	0.087	Stabilizing	0.995	D	0.523	neutral	N	0.467103911	None	None	N
D/I	0.4692	ambiguous	0.4736	ambiguous	0.274	Stabilizing	0.995	D	0.641	neutral	None	None	None	None	N
D/K	0.5021	ambiguous	0.5158	ambiguous	0.372	Stabilizing	0.896	D	0.479	neutral	None	None	None	None	N
D/L	0.4821	ambiguous	0.4847	ambiguous	0.274	Stabilizing	0.984	D	0.626	neutral	None	None	None	None	N
D/M	0.6593	likely_pathogenic	0.6677	pathogenic	0.362	Stabilizing	0.996	D	0.651	neutral	None	None	None	None	N
D/N	0.1155	likely_benign	0.108	benign	-0.101	Destabilizing	0.447	N	0.507	neutral	N	0.445400487	None	None	N
D/P	0.7525	likely_pathogenic	0.7111	pathogenic	0.111	Stabilizing	0.786	D	0.511	neutral	None	None	None	None	N
D/Q	0.3788	ambiguous	0.3992	ambiguous	-0.036	Destabilizing	0.919	D	0.475	neutral	None	None	None	None	N
D/R	0.5111	ambiguous	0.527	ambiguous	0.557	Stabilizing	0.968	D	0.599	neutral	None	None	None	None	N
D/S	0.1337	likely_benign	0.13	benign	-0.187	Destabilizing	0.706	D	0.491	neutral	None	None	None	None	N
D/T	0.2474	likely_benign	0.2512	benign	0.001	Stabilizing	0.884	D	0.48	neutral	None	None	None	None	N
D/V	0.2737	likely_benign	0.2794	benign	0.111	Stabilizing	0.89	D	0.617	neutral	N	0.390795211	None	None	N
D/W	0.9122	likely_pathogenic	0.9132	pathogenic	0.121	Stabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
D/Y	0.3311	likely_benign	0.3209	benign	0.197	Stabilizing	0.998	D	0.629	neutral	N	0.462698169	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.