TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33371	100336;100337;100338	chr2:178536998;178536997;178536996	chr2:179401725;179401724;179401723
N2AB	31730	95413;95414;95415	chr2:178536998;178536997;178536996	chr2:179401725;179401724;179401723
N2A	30803	92632;92633;92634	chr2:178536998;178536997;178536996	chr2:179401725;179401724;179401723
N2B	24306	73141;73142;73143	chr2:178536998;178536997;178536996	chr2:179401725;179401724;179401723
Novex-1	24431	73516;73517;73518	chr2:178536998;178536997;178536996	chr2:179401725;179401724;179401723
Novex-2	24498	73717;73718;73719	chr2:178536998;178536997;178536996	chr2:179401725;179401724;179401723
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-130
• Domain position: 82
• Structural Position: 113
• Q(SASA): 0.6878
• 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	rs2154137940	None	0.062	N	0.433	0.07	0.177238962908	gnomAD-4.0.0	3.1849E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8599E-06	1.43484E-05	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	0.1113	likely_benign	0.0807	benign	-0.505	Destabilizing	0.027	N	0.365	neutral	N	0.389437269	None	None	I
T/C	0.5027	ambiguous	0.3907	ambiguous	-0.296	Destabilizing	0.935	D	0.379	neutral	None	None	None	None	I
T/D	0.6095	likely_pathogenic	0.514	ambiguous	0.38	Stabilizing	0.149	N	0.46	neutral	None	None	None	None	I
T/E	0.5046	ambiguous	0.4071	ambiguous	0.302	Stabilizing	0.035	N	0.433	neutral	None	None	None	None	I
T/F	0.5302	ambiguous	0.3922	ambiguous	-1.034	Destabilizing	0.38	N	0.493	neutral	None	None	None	None	I
T/G	0.3847	ambiguous	0.3039	benign	-0.619	Destabilizing	0.149	N	0.484	neutral	None	None	None	None	I
T/H	0.3792	ambiguous	0.2822	benign	-0.877	Destabilizing	0.555	D	0.451	neutral	None	None	None	None	I
T/I	0.2323	likely_benign	0.1578	benign	-0.323	Destabilizing	0.062	N	0.433	neutral	N	0.391690927	None	None	I
T/K	0.3228	likely_benign	0.2224	benign	-0.273	Destabilizing	0.081	N	0.434	neutral	None	None	None	None	I
T/L	0.1575	likely_benign	0.1038	benign	-0.323	Destabilizing	None	N	0.162	neutral	None	None	None	None	I
T/M	0.1681	likely_benign	0.1091	benign	-0.099	Destabilizing	0.005	N	0.325	neutral	None	None	None	None	I
T/N	0.1766	likely_benign	0.1219	benign	-0.056	Destabilizing	0.211	N	0.318	neutral	N	0.439327372	None	None	I
T/P	0.1573	likely_benign	0.145	benign	-0.356	Destabilizing	0.741	D	0.405	neutral	N	0.410911406	None	None	I
T/Q	0.2844	likely_benign	0.1993	benign	-0.291	Destabilizing	0.003	N	0.133	neutral	None	None	None	None	I
T/R	0.2595	likely_benign	0.1762	benign	-0.004	Destabilizing	0.149	N	0.447	neutral	None	None	None	None	I
T/S	0.1808	likely_benign	0.1323	benign	-0.328	Destabilizing	0.052	N	0.377	neutral	N	0.393536367	None	None	I
T/V	0.1871	likely_benign	0.1393	benign	-0.356	Destabilizing	0.035	N	0.349	neutral	None	None	None	None	I
T/W	0.8021	likely_pathogenic	0.7361	pathogenic	-1.001	Destabilizing	0.935	D	0.448	neutral	None	None	None	None	I
T/Y	0.4148	ambiguous	0.3413	ambiguous	-0.726	Destabilizing	0.555	D	0.488	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.