TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19475	58648;58649;58650	chr2:178593970;178593969;178593968	chr2:179458697;179458696;179458695
N2AB	17834	53725;53726;53727	chr2:178593970;178593969;178593968	chr2:179458697;179458696;179458695
N2A	16907	50944;50945;50946	chr2:178593970;178593969;178593968	chr2:179458697;179458696;179458695
N2B	10410	31453;31454;31455	chr2:178593970;178593969;178593968	chr2:179458697;179458696;179458695
Novex-1	10535	31828;31829;31830	chr2:178593970;178593969;178593968	chr2:179458697;179458696;179458695
Novex-2	10602	32029;32030;32031	chr2:178593970;178593969;178593968	chr2:179458697;179458696;179458695
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-118
• Domain position: 85
• Structural Position: 175
• Q(SASA): 0.5352
• 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
N/H	None	None	0.56	N	0.409	0.157	0.287603790349	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
N/S	rs755738851	0.015	0.001	N	0.09	0.07	0.200317383148	gnomAD-2.1.1	1.43E-05	None	None	None	None	N	None	8.26E-05	0	None	0	0	None	0	None	0	0	2.81215E-04
N/S	rs755738851	0.015	0.001	N	0.09	0.07	0.200317383148	gnomAD-4.0.0	4.10627E-06	None	None	None	None	N	None	1.19567E-04	0	None	0	0	None	0	3.47222E-04	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
N/A	0.1751	likely_benign	0.2127	benign	-0.754	Destabilizing	None	N	0.203	neutral	None	None	None	None	N
N/C	0.2341	likely_benign	0.2647	benign	0.071	Stabilizing	0.676	D	0.463	neutral	None	None	None	None	N
N/D	0.1365	likely_benign	0.1401	benign	-0.381	Destabilizing	0.055	N	0.265	neutral	N	0.477800907	None	None	N
N/E	0.3139	likely_benign	0.3121	benign	-0.345	Destabilizing	0.072	N	0.245	neutral	None	None	None	None	N
N/F	0.3872	ambiguous	0.4254	ambiguous	-0.759	Destabilizing	0.356	N	0.485	neutral	None	None	None	None	N
N/G	0.3634	ambiguous	0.3996	ambiguous	-1.027	Destabilizing	0.016	N	0.332	neutral	None	None	None	None	N
N/H	0.0991	likely_benign	0.1055	benign	-0.877	Destabilizing	0.56	D	0.409	neutral	N	0.484342877	None	None	N
N/I	0.1231	likely_benign	0.1391	benign	-0.088	Destabilizing	0.029	N	0.486	neutral	N	0.454366687	None	None	N
N/K	0.3081	likely_benign	0.3059	benign	-0.119	Destabilizing	0.055	N	0.24	neutral	N	0.446187134	None	None	N
N/L	0.1686	likely_benign	0.1851	benign	-0.088	Destabilizing	0.016	N	0.468	neutral	None	None	None	None	N
N/M	0.1891	likely_benign	0.2143	benign	0.465	Stabilizing	0.356	N	0.433	neutral	None	None	None	None	N
N/P	0.9323	likely_pathogenic	0.9266	pathogenic	-0.281	Destabilizing	0.072	N	0.453	neutral	None	None	None	None	N
N/Q	0.303	likely_benign	0.3245	benign	-0.793	Destabilizing	0.356	N	0.369	neutral	None	None	None	None	N
N/R	0.3291	likely_benign	0.3199	benign	-0.041	Destabilizing	0.072	N	0.351	neutral	None	None	None	None	N
N/S	0.0758	likely_benign	0.084	benign	-0.646	Destabilizing	0.001	N	0.09	neutral	N	0.453499896	None	None	N
N/T	0.0734	likely_benign	0.0833	benign	-0.433	Destabilizing	None	N	0.095	neutral	N	0.403359077	None	None	N
N/V	0.1341	likely_benign	0.1542	benign	-0.281	Destabilizing	0.038	N	0.475	neutral	None	None	None	None	N
N/W	0.6625	likely_pathogenic	0.6791	pathogenic	-0.531	Destabilizing	0.864	D	0.528	neutral	None	None	None	None	N
N/Y	0.1559	likely_benign	0.169	benign	-0.323	Destabilizing	0.295	N	0.443	neutral	N	0.485478974	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.