TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5422	16489;16490;16491	chr2:178732912;178732911;178732910	chr2:179597639;179597638;179597637
N2AB	5105	15538;15539;15540	chr2:178732912;178732911;178732910	chr2:179597639;179597638;179597637
N2A	4178	12757;12758;12759	chr2:178732912;178732911;178732910	chr2:179597639;179597638;179597637
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-37
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.791
• 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
N/K	rs762625771	0.683	0.029	N	0.245	0.084	0.0297737177859	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/K	rs762625771	0.683	0.029	N	0.245	0.084	0.0297737177859	gnomAD-4.0.0	6.00203E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.25036E-06	0	3.66381E-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
N/A	0.0843	likely_benign	0.0967	benign	-0.209	Destabilizing	None	N	0.159	neutral	None	None	None	None	I
N/C	0.1806	likely_benign	0.204	benign	0.464	Stabilizing	0.676	D	0.305	neutral	None	None	None	None	I
N/D	0.0775	likely_benign	0.0865	benign	0.059	Stabilizing	0.012	N	0.263	neutral	N	0.388385971	None	None	I
N/E	0.1483	likely_benign	0.1809	benign	0.004	Stabilizing	0.038	N	0.241	neutral	None	None	None	None	I
N/F	0.2875	likely_benign	0.3497	ambiguous	-0.709	Destabilizing	0.356	N	0.343	neutral	None	None	None	None	I
N/G	0.1127	likely_benign	0.1228	benign	-0.34	Destabilizing	0.016	N	0.272	neutral	None	None	None	None	I
N/H	0.0799	likely_benign	0.087	benign	-0.435	Destabilizing	0.295	N	0.318	neutral	N	0.451610731	None	None	I
N/I	0.1298	likely_benign	0.1578	benign	0.046	Stabilizing	0.171	N	0.365	neutral	N	0.45599783	None	None	I
N/K	0.1141	likely_benign	0.1318	benign	0.163	Stabilizing	0.029	N	0.245	neutral	N	0.423634696	None	None	I
N/L	0.1237	likely_benign	0.1412	benign	0.046	Stabilizing	0.038	N	0.363	neutral	None	None	None	None	I
N/M	0.1695	likely_benign	0.1985	benign	0.378	Stabilizing	0.356	N	0.293	neutral	None	None	None	None	I
N/P	0.3288	likely_benign	0.373	ambiguous	-0.014	Destabilizing	0.072	N	0.355	neutral	None	None	None	None	I
N/Q	0.1432	likely_benign	0.1624	benign	-0.148	Destabilizing	0.214	N	0.294	neutral	None	None	None	None	I
N/R	0.127	likely_benign	0.1494	benign	0.23	Stabilizing	0.072	N	0.297	neutral	None	None	None	None	I
N/S	0.0547	likely_benign	0.0578	benign	0.091	Stabilizing	None	N	0.085	neutral	N	0.315619009	None	None	I
N/T	0.0691	likely_benign	0.0759	benign	0.157	Stabilizing	None	N	0.109	neutral	N	0.36374103	None	None	I
N/V	0.1301	likely_benign	0.1552	benign	-0.014	Destabilizing	0.038	N	0.364	neutral	None	None	None	None	I
N/W	0.4209	ambiguous	0.5016	ambiguous	-0.778	Destabilizing	0.864	D	0.361	neutral	None	None	None	None	I
N/Y	0.113	likely_benign	0.133	benign	-0.483	Destabilizing	0.295	N	0.31	neutral	N	0.445223476	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.