TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27848	83767;83768;83769	chr2:178562590;178562589;178562588	chr2:179427317;179427316;179427315
N2AB	26207	78844;78845;78846	chr2:178562590;178562589;178562588	chr2:179427317;179427316;179427315
N2A	25280	76063;76064;76065	chr2:178562590;178562589;178562588	chr2:179427317;179427316;179427315
N2B	18783	56572;56573;56574	chr2:178562590;178562589;178562588	chr2:179427317;179427316;179427315
Novex-1	18908	56947;56948;56949	chr2:178562590;178562589;178562588	chr2:179427317;179427316;179427315
Novex-2	18975	57148;57149;57150	chr2:178562590;178562589;178562588	chr2:179427317;179427316;179427315
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-90
• Domain position: 83
• Structural Position: 117
• Q(SASA): 0.6349
• 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
I/T	rs397517723	-0.433	0.003	N	0.465	0.118	0.52170519339	gnomAD-2.1.1	1.22E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	2.68E-05	0
I/T	rs397517723	-0.433	0.003	N	0.465	0.118	0.52170519339	gnomAD-4.0.0	4.11295E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.4013E-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
I/A	0.1816	likely_benign	0.1998	benign	-0.765	Destabilizing	None	N	0.317	neutral	None	None	None	None	I
I/C	0.5778	likely_pathogenic	0.6162	pathogenic	-0.869	Destabilizing	0.32	N	0.529	neutral	None	None	None	None	I
I/D	0.7096	likely_pathogenic	0.7685	pathogenic	0.558	Stabilizing	0.32	N	0.55	neutral	None	None	None	None	I
I/E	0.5891	likely_pathogenic	0.6478	pathogenic	0.513	Stabilizing	0.047	N	0.56	neutral	None	None	None	None	I
I/F	0.1753	likely_benign	0.2069	benign	-0.618	Destabilizing	0.02	N	0.475	neutral	N	0.515921286	None	None	I
I/G	0.5779	likely_pathogenic	0.6236	pathogenic	-0.962	Destabilizing	0.032	N	0.524	neutral	None	None	None	None	I
I/H	0.5651	likely_pathogenic	0.6299	pathogenic	-0.216	Destabilizing	0.692	D	0.553	neutral	None	None	None	None	I
I/K	0.4662	ambiguous	0.5548	ambiguous	-0.167	Destabilizing	0.002	N	0.529	neutral	None	None	None	None	I
I/L	0.1171	likely_benign	0.1296	benign	-0.352	Destabilizing	None	N	0.243	neutral	N	0.476536179	None	None	I
I/M	0.1089	likely_benign	0.1136	benign	-0.464	Destabilizing	None	N	0.251	neutral	N	0.510958184	None	None	I
I/N	0.3158	likely_benign	0.3635	ambiguous	-0.029	Destabilizing	0.262	N	0.559	neutral	D	0.522961902	None	None	I
I/P	0.4284	ambiguous	0.4704	ambiguous	-0.457	Destabilizing	0.32	N	0.549	neutral	None	None	None	None	I
I/Q	0.4676	ambiguous	0.5166	ambiguous	-0.167	Destabilizing	0.163	N	0.559	neutral	None	None	None	None	I
I/R	0.3476	ambiguous	0.4298	ambiguous	0.228	Stabilizing	0.158	N	0.549	neutral	None	None	None	None	I
I/S	0.2408	likely_benign	0.2713	benign	-0.693	Destabilizing	0.024	N	0.519	neutral	N	0.510822111	None	None	I
I/T	0.0951	likely_benign	0.1092	benign	-0.615	Destabilizing	0.003	N	0.465	neutral	N	0.494929939	None	None	I
I/V	0.0553	likely_benign	0.061	benign	-0.457	Destabilizing	None	N	0.193	neutral	N	0.420856254	None	None	I
I/W	0.7852	likely_pathogenic	0.8065	pathogenic	-0.582	Destabilizing	0.89	D	0.559	neutral	None	None	None	None	I
I/Y	0.538	ambiguous	0.5966	pathogenic	-0.326	Destabilizing	0.021	N	0.529	neutral	None	None	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.