TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27663	83212;83213;83214	chr2:178563145;178563144;178563143	chr2:179427872;179427871;179427870
N2AB	26022	78289;78290;78291	chr2:178563145;178563144;178563143	chr2:179427872;179427871;179427870
N2A	25095	75508;75509;75510	chr2:178563145;178563144;178563143	chr2:179427872;179427871;179427870
N2B	18598	56017;56018;56019	chr2:178563145;178563144;178563143	chr2:179427872;179427871;179427870
Novex-1	18723	56392;56393;56394	chr2:178563145;178563144;178563143	chr2:179427872;179427871;179427870
Novex-2	18790	56593;56594;56595	chr2:178563145;178563144;178563143	chr2:179427872;179427871;179427870
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-89
• Domain position: 94
• Structural Position: 126
• Q(SASA): 0.3436
• 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
S/L	None	None	0.376	N	0.692	0.206	0.603223074362	gnomAD-4.0.0	1.59145E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85878E-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
S/A	0.06	likely_benign	0.0616	benign	-0.455	Destabilizing	0.004	N	0.217	neutral	N	0.459732434	None	None	N
S/C	0.0909	likely_benign	0.0949	benign	-0.347	Destabilizing	0.977	D	0.635	neutral	None	None	None	None	N
S/D	0.3497	ambiguous	0.3608	ambiguous	0.02	Stabilizing	0.615	D	0.522	neutral	None	None	None	None	N
S/E	0.3801	ambiguous	0.3743	ambiguous	-0.074	Destabilizing	0.615	D	0.513	neutral	None	None	None	None	N
S/F	0.1625	likely_benign	0.1592	benign	-1.022	Destabilizing	0.919	D	0.766	deleterious	None	None	None	None	N
S/G	0.0925	likely_benign	0.0891	benign	-0.568	Destabilizing	0.444	N	0.483	neutral	None	None	None	None	N
S/H	0.2557	likely_benign	0.2528	benign	-1.092	Destabilizing	0.992	D	0.636	neutral	None	None	None	None	N
S/I	0.1184	likely_benign	0.1192	benign	-0.285	Destabilizing	0.848	D	0.729	deleterious	None	None	None	None	N
S/K	0.3798	ambiguous	0.3948	ambiguous	-0.507	Destabilizing	0.615	D	0.515	neutral	None	None	None	None	N
S/L	0.0791	likely_benign	0.0788	benign	-0.285	Destabilizing	0.376	N	0.692	prob.delet.	N	0.494789158	None	None	N
S/M	0.1405	likely_benign	0.1491	benign	0.035	Stabilizing	0.992	D	0.639	neutral	None	None	None	None	N
S/N	0.1054	likely_benign	0.1122	benign	-0.255	Destabilizing	0.615	D	0.567	neutral	None	None	None	None	N
S/P	0.0775	likely_benign	0.0795	benign	-0.313	Destabilizing	0.004	N	0.292	neutral	N	0.389853849	None	None	N
S/Q	0.3208	likely_benign	0.3316	benign	-0.555	Destabilizing	0.919	D	0.55	neutral	None	None	None	None	N
S/R	0.3541	ambiguous	0.3548	ambiguous	-0.276	Destabilizing	0.848	D	0.642	neutral	None	None	None	None	N
S/T	0.0656	likely_benign	0.0698	benign	-0.372	Destabilizing	0.016	N	0.292	neutral	N	0.423889064	None	None	N
S/V	0.1073	likely_benign	0.1143	benign	-0.313	Destabilizing	0.444	N	0.7	prob.delet.	None	None	None	None	N
S/W	0.3333	likely_benign	0.2826	benign	-0.987	Destabilizing	0.992	D	0.795	deleterious	None	None	None	None	N
S/Y	0.1769	likely_benign	0.1566	benign	-0.721	Destabilizing	0.972	D	0.775	deleterious	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.