TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9423	28492;28493;28494	chr2:178710830;178710829;178710828	chr2:179575557;179575556;179575555
N2AB	9106	27541;27542;27543	chr2:178710830;178710829;178710828	chr2:179575557;179575556;179575555
N2A	8179	24760;24761;24762	chr2:178710830;178710829;178710828	chr2:179575557;179575556;179575555
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-80
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.5969
• 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
T/I	None	None	0.669	None	0.443	0.355	0.508398094826	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
T/A	0.1205	likely_benign	0.1671	benign	-0.342	Destabilizing	0.454	N	0.334	neutral	None	None	None	None	I
T/C	0.6839	likely_pathogenic	0.8147	pathogenic	-0.3	Destabilizing	0.998	D	0.419	neutral	None	None	None	None	I
T/D	0.5136	ambiguous	0.6311	pathogenic	0.074	Stabilizing	0.842	D	0.443	neutral	None	None	None	None	I
T/E	0.4737	ambiguous	0.5776	pathogenic	0.027	Stabilizing	0.842	D	0.441	neutral	None	None	None	None	I
T/F	0.33	likely_benign	0.4665	ambiguous	-0.638	Destabilizing	0.949	D	0.562	neutral	None	None	None	None	I
T/G	0.3423	ambiguous	0.4521	ambiguous	-0.524	Destabilizing	0.728	D	0.511	neutral	None	None	None	None	I
T/H	0.4204	ambiguous	0.5225	ambiguous	-0.768	Destabilizing	0.998	D	0.541	neutral	None	None	None	None	I
T/I	0.3361	likely_benign	0.5059	ambiguous	0.026	Stabilizing	0.669	D	0.443	neutral	None	None	None	None	I
T/K	0.3891	ambiguous	0.5109	ambiguous	-0.528	Destabilizing	0.801	D	0.418	neutral	None	None	None	None	I
T/L	0.1837	likely_benign	0.2631	benign	0.026	Stabilizing	0.016	N	0.301	neutral	None	None	None	None	I
T/M	0.1427	likely_benign	0.1746	benign	0.052	Stabilizing	0.949	D	0.423	neutral	None	None	None	None	I
T/N	0.1678	likely_benign	0.2348	benign	-0.302	Destabilizing	0.842	D	0.383	neutral	None	None	None	None	I
T/P	0.2656	likely_benign	0.3816	ambiguous	-0.066	Destabilizing	0.966	D	0.428	neutral	None	None	None	None	I
T/Q	0.3571	ambiguous	0.4506	ambiguous	-0.472	Destabilizing	0.974	D	0.436	neutral	None	None	None	None	I
T/R	0.3005	likely_benign	0.3944	ambiguous	-0.263	Destabilizing	0.934	D	0.433	neutral	None	None	None	None	I
T/S	0.1108	likely_benign	0.1267	benign	-0.507	Destabilizing	0.022	N	0.191	neutral	None	None	None	None	I
T/V	0.2608	likely_benign	0.3985	ambiguous	-0.066	Destabilizing	0.728	D	0.314	neutral	None	None	None	None	I
T/W	0.713	likely_pathogenic	0.7884	pathogenic	-0.663	Destabilizing	0.998	D	0.591	neutral	None	None	None	None	I
T/Y	0.4124	ambiguous	0.5569	ambiguous	-0.396	Destabilizing	0.991	D	0.553	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.