TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10007	30244;30245;30246	chr2:178704351;178704350;178704349	chr2:179569078;179569077;179569076
N2AB	9690	29293;29294;29295	chr2:178704351;178704350;178704349	chr2:179569078;179569077;179569076
N2A	8763	26512;26513;26514	chr2:178704351;178704350;178704349	chr2:179569078;179569077;179569076
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: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-85
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.4095
• 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/N	rs1168557032	None	0.81	None	0.531	0.156	0.263612267334	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	7.32654E-05

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	0.1335	likely_benign	0.134	benign	-0.557	Destabilizing	0.201	N	0.539	neutral	None	None	None	None	N
T/C	0.6924	likely_pathogenic	0.7315	pathogenic	-0.265	Destabilizing	0.026	N	0.469	neutral	None	None	None	None	N
T/D	0.6276	likely_pathogenic	0.6527	pathogenic	-0.08	Destabilizing	0.447	N	0.456	neutral	None	None	None	None	N
T/E	0.3957	ambiguous	0.4005	ambiguous	-0.119	Destabilizing	0.048	N	0.421	neutral	None	None	None	None	N
T/F	0.3826	ambiguous	0.4159	ambiguous	-0.773	Destabilizing	0.85	D	0.571	neutral	None	None	None	None	N
T/G	0.5575	ambiguous	0.5921	pathogenic	-0.769	Destabilizing	0.447	N	0.499	neutral	None	None	None	None	N
T/H	0.3587	ambiguous	0.401	ambiguous	-1.06	Destabilizing	0.992	D	0.575	neutral	None	None	None	None	N
T/I	0.1806	likely_benign	0.2058	benign	-0.099	Destabilizing	0.681	D	0.519	neutral	None	None	None	None	N
T/K	0.2987	likely_benign	0.3301	benign	-0.614	Destabilizing	0.617	D	0.457	neutral	None	None	None	None	N
T/L	0.1589	likely_benign	0.1837	benign	-0.099	Destabilizing	0.103	N	0.506	neutral	None	None	None	None	N
T/M	0.1208	likely_benign	0.1275	benign	0.164	Stabilizing	0.103	N	0.468	neutral	None	None	None	None	N
T/N	0.24	likely_benign	0.27	benign	-0.395	Destabilizing	0.81	D	0.531	neutral	None	None	None	None	N
T/P	0.5506	ambiguous	0.5797	pathogenic	-0.22	Destabilizing	0.896	D	0.536	neutral	None	None	None	None	N
T/Q	0.2899	likely_benign	0.3075	benign	-0.603	Destabilizing	0.85	D	0.537	neutral	None	None	None	None	N
T/R	0.2246	likely_benign	0.2434	benign	-0.328	Destabilizing	0.85	D	0.536	neutral	None	None	None	None	N
T/S	0.1748	likely_benign	0.1924	benign	-0.633	Destabilizing	0.016	N	0.496	neutral	None	None	None	None	N
T/V	0.1527	likely_benign	0.17	benign	-0.22	Destabilizing	0.447	N	0.537	neutral	None	None	None	None	N
T/W	0.7766	likely_pathogenic	0.8009	pathogenic	-0.74	Destabilizing	0.992	D	0.608	neutral	None	None	None	None	N
T/Y	0.4766	ambiguous	0.5231	ambiguous	-0.502	Destabilizing	0.92	D	0.567	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.