TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14912	44959;44960;44961	chr2:178624546;178624545;178624544	chr2:179489273;179489272;179489271
N2AB	13271	40036;40037;40038	chr2:178624546;178624545;178624544	chr2:179489273;179489272;179489271
N2A	12344	37255;37256;37257	chr2:178624546;178624545;178624544	chr2:179489273;179489272;179489271
N2B	5847	17764;17765;17766	chr2:178624546;178624545;178624544	chr2:179489273;179489272;179489271
Novex-1	5972	18139;18140;18141	chr2:178624546;178624545;178624544	chr2:179489273;179489272;179489271
Novex-2	6039	18340;18341;18342	chr2:178624546;178624545;178624544	chr2:179489273;179489272;179489271
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-100
• Domain position: 60
• Structural Position: 141
• Q(SASA): 0.6019
• 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
H/P	rs2058749191	None	0.989	N	0.557	0.34	0.548571244948	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
H/P	rs2058749191	None	0.989	N	0.557	0.34	0.548571244948	gnomAD-4.0.0	2.0302E-06	None	None	None	None	N	None	3.49491E-05	0	None	0	0	None	0	0	0	0	0
H/Q	rs762830792	0.438	0.934	N	0.431	0.3	0.12205267543	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	5.81E-05	None	0	0	None	0	None	0	0	0
H/Q	rs762830792	0.438	0.934	N	0.431	0.3	0.12205267543	gnomAD-4.0.0	1.36921E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79972E-06	0	0
H/R	None	None	0.012	N	0.181	0.157	0.302459207581	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-06	0	0
H/Y	rs766391823	0.98	0.012	N	0.162	0.216	None	gnomAD-2.1.1	5.73E-05	None	None	None	None	N	None	4.14E-05	1.1343E-04	None	3.87147E-04	0	None	0	None	0	5.49E-05	0
H/Y	rs766391823	0.98	0.012	N	0.162	0.216	None	gnomAD-3.1.2	8.55E-05	None	None	None	None	N	None	2.41E-05	4.59861E-04	0	8.64553E-04	0	None	0	0	2.94E-05	0	0
H/Y	rs766391823	0.98	0.012	N	0.162	0.216	None	gnomAD-4.0.0	5.58088E-05	None	None	None	None	N	None	1.33608E-05	1.83688E-04	None	5.07237E-04	0	None	0	0	4.91851E-05	0	8.0141E-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	0.2932	likely_benign	0.3733	ambiguous	-0.46	Destabilizing	0.842	D	0.468	neutral	None	None	None	None	N
H/C	0.2049	likely_benign	0.2078	benign	0.31	Stabilizing	0.998	D	0.577	neutral	None	None	None	None	N
H/D	0.3018	likely_benign	0.3212	benign	-0.318	Destabilizing	0.966	D	0.445	neutral	N	0.492594554	None	None	N
H/E	0.2984	likely_benign	0.3351	benign	-0.244	Destabilizing	0.842	D	0.375	neutral	None	None	None	None	N
H/F	0.3575	ambiguous	0.4038	ambiguous	0.394	Stabilizing	0.904	D	0.449	neutral	None	None	None	None	N
H/G	0.3227	likely_benign	0.3687	ambiguous	-0.807	Destabilizing	0.915	D	0.499	neutral	None	None	None	None	N
H/I	0.3381	likely_benign	0.4034	ambiguous	0.479	Stabilizing	0.949	D	0.575	neutral	None	None	None	None	N
H/K	0.1442	likely_benign	0.1712	benign	-0.323	Destabilizing	0.728	D	0.396	neutral	None	None	None	None	N
H/L	0.1323	likely_benign	0.1487	benign	0.479	Stabilizing	0.669	D	0.51	neutral	N	0.471590639	None	None	N
H/M	0.4434	ambiguous	0.5336	ambiguous	0.393	Stabilizing	0.998	D	0.538	neutral	None	None	None	None	N
H/N	0.1195	likely_benign	0.1356	benign	-0.245	Destabilizing	0.801	D	0.469	neutral	N	0.442552334	None	None	N
H/P	0.2674	likely_benign	0.2931	benign	0.188	Stabilizing	0.989	D	0.557	neutral	N	0.499406092	None	None	N
H/Q	0.153	likely_benign	0.1811	benign	-0.038	Destabilizing	0.934	D	0.431	neutral	N	0.492979428	None	None	N
H/R	0.0738	likely_benign	0.0718	benign	-0.829	Destabilizing	0.012	N	0.181	neutral	N	0.454887187	None	None	N
H/S	0.2301	likely_benign	0.2809	benign	-0.267	Destabilizing	0.842	D	0.449	neutral	None	None	None	None	N
H/T	0.2269	likely_benign	0.3077	benign	-0.096	Destabilizing	0.974	D	0.483	neutral	None	None	None	None	N
H/V	0.2896	likely_benign	0.3592	ambiguous	0.188	Stabilizing	0.949	D	0.498	neutral	None	None	None	None	N
H/W	0.3488	ambiguous	0.3498	ambiguous	0.506	Stabilizing	0.993	D	0.544	neutral	None	None	None	None	N
H/Y	0.1185	likely_benign	0.1235	benign	0.761	Stabilizing	0.012	N	0.162	neutral	N	0.49977608	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.