TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14501	43726;43727;43728	chr2:178632393;178632392;178632391	chr2:179497120;179497119;179497118
N2AB	12860	38803;38804;38805	chr2:178632393;178632392;178632391	chr2:179497120;179497119;179497118
N2A	11933	36022;36023;36024	chr2:178632393;178632392;178632391	chr2:179497120;179497119;179497118
N2B	5436	16531;16532;16533	chr2:178632393;178632392;178632391	chr2:179497120;179497119;179497118
Novex-1	5561	16906;16907;16908	chr2:178632393;178632392;178632391	chr2:179497120;179497119;179497118
Novex-2	5628	17107;17108;17109	chr2:178632393;178632392;178632391	chr2:179497120;179497119;179497118
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-96
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.2206
• 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
T/A	rs764500643	-0.624	0.005	N	0.112	0.134	None	gnomAD-2.1.1	3.54E-05	None	None	None	None	N	None	3.90761E-04	0	None	0	0	None	0	None	0	0	0
T/A	rs764500643	-0.624	0.005	N	0.112	0.134	None	gnomAD-3.1.2	5.93E-05	None	None	None	None	N	None	2.17633E-04	0	0	0	0	None	0	0	0	0	0
T/A	rs764500643	-0.624	0.005	N	0.112	0.134	None	gnomAD-4.0.0	1.25638E-05	None	None	None	None	N	None	2.70205E-04	0	None	0	0	None	0	0	0	0	0
T/I	rs115825044	0.197	0.934	N	0.441	0.248	0.459642846412	gnomAD-2.1.1	1.78E-05	None	None	None	None	N	None	0	9.87E-05	None	0	0	None	0	None	0	9.8E-06	0
T/I	rs115825044	0.197	0.934	N	0.441	0.248	0.459642846412	gnomAD-4.0.0	2.08197E-06	None	None	None	None	N	None	0	4.85555E-05	None	0	0	None	0	0	9.06645E-07	0	0
T/N	None	-0.324	0.891	N	0.368	0.213	0.403328974453	gnomAD-2.1.1	5.08E-05	None	None	None	None	N	None	0	0	None	0	6.19369E-04	None	0	None	0	1.7E-05	0
T/N	None	-0.324	0.891	N	0.368	0.213	0.403328974453	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	2.41E-05	0	0	0	1.93648E-04	None	0	0	0	0	0
T/N	None	-0.324	0.891	N	0.368	0.213	0.403328974453	gnomAD-4.0.0	1.1928E-05	None	None	None	None	N	None	1.34953E-05	0	None	0	2.93507E-04	None	0	0	4.27009E-06	0	0
T/S	rs115825044	-0.651	0.454	N	0.373	0.211	0.156986980423	gnomAD-2.1.1	1.21208E-04	None	None	None	None	N	None	1.03645E-03	9.61E-05	None	0	0	None	0	None	0	8.51E-06	4.55512E-04
T/S	rs115825044	-0.651	0.454	N	0.373	0.211	0.156986980423	gnomAD-3.1.2	4.14626E-04	None	None	None	None	N	None	1.23165E-03	4.59619E-04	0	0	0	None	0	0	4.41E-05	0	9.61538E-04
T/S	rs115825044	-0.651	0.454	N	0.373	0.211	0.156986980423	1000 genomes	9.98403E-04	None	None	None	None	N	None	3E-03	1.4E-03	None	None	0	0	None	None	None	0	None
T/S	rs115825044	-0.651	0.454	N	0.373	0.211	0.156986980423	gnomAD-4.0.0	1.04206E-04	None	None	None	None	N	None	1.29345E-03	2.12615E-04	None	0	0	None	0	8.35561E-04	3.15989E-05	0	2.59648E-04

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
T/A	0.1173	likely_benign	0.1046	benign	-0.701	Destabilizing	0.005	N	0.112	neutral	N	0.490259585	None	None	N
T/C	0.6078	likely_pathogenic	0.5397	ambiguous	-0.48	Destabilizing	0.998	D	0.413	neutral	None	None	None	None	N
T/D	0.4888	ambiguous	0.4434	ambiguous	0.06	Stabilizing	0.915	D	0.421	neutral	None	None	None	None	N
T/E	0.2986	likely_benign	0.2764	benign	0.075	Stabilizing	0.842	D	0.393	neutral	None	None	None	None	N
T/F	0.2967	likely_benign	0.2727	benign	-0.678	Destabilizing	0.991	D	0.526	neutral	None	None	None	None	N
T/G	0.4994	ambiguous	0.4314	ambiguous	-0.971	Destabilizing	0.728	D	0.435	neutral	None	None	None	None	N
T/H	0.2512	likely_benign	0.2114	benign	-1.151	Destabilizing	0.991	D	0.505	neutral	None	None	None	None	N
T/I	0.1944	likely_benign	0.1796	benign	-0.074	Destabilizing	0.934	D	0.441	neutral	N	0.511629832	None	None	N
T/K	0.1709	likely_benign	0.1442	benign	-0.61	Destabilizing	0.029	N	0.185	neutral	None	None	None	None	N
T/L	0.1281	likely_benign	0.1163	benign	-0.074	Destabilizing	0.842	D	0.399	neutral	None	None	None	None	N
T/M	0.1088	likely_benign	0.1043	benign	0.016	Stabilizing	0.991	D	0.429	neutral	None	None	None	None	N
T/N	0.1434	likely_benign	0.1256	benign	-0.589	Destabilizing	0.891	D	0.368	neutral	N	0.513236722	None	None	N
T/P	0.4605	ambiguous	0.4064	ambiguous	-0.25	Destabilizing	0.966	D	0.439	neutral	N	0.514823397	None	None	N
T/Q	0.2141	likely_benign	0.1877	benign	-0.694	Destabilizing	0.949	D	0.443	neutral	None	None	None	None	N
T/R	0.1422	likely_benign	0.1222	benign	-0.41	Destabilizing	0.016	N	0.24	neutral	None	None	None	None	N
T/S	0.1599	likely_benign	0.1372	benign	-0.897	Destabilizing	0.454	N	0.373	neutral	N	0.411580873	None	None	N
T/V	0.1801	likely_benign	0.1684	benign	-0.25	Destabilizing	0.728	D	0.31	neutral	None	None	None	None	N
T/W	0.7318	likely_pathogenic	0.6845	pathogenic	-0.627	Destabilizing	0.998	D	0.543	neutral	None	None	None	None	N
T/Y	0.3282	likely_benign	0.2933	benign	-0.386	Destabilizing	0.991	D	0.526	neutral	None	None	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.