TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5702	17329;17330;17331	chr2:178731771;178731770;178731769	chr2:179596498;179596497;179596496
N2AB	5385	16378;16379;16380	chr2:178731771;178731770;178731769	chr2:179596498;179596497;179596496
N2A	4458	13597;13598;13599	chr2:178731771;178731770;178731769	chr2:179596498;179596497;179596496
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-40
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.4523
• 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
A/T	rs2080567900	None	None	N	0.089	0.078	0.0401082797425	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
A/T	rs2080567900	None	None	N	0.089	0.078	0.0401082797425	gnomAD-4.0.0	6.57203E-06	None	None	None	None	I	None	2.41301E-05	0	None	0	0	None	0	0	0	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
A/C	0.4175	ambiguous	0.3346	benign	-0.784	Destabilizing	0.676	D	0.382	neutral	None	None	None	None	I
A/D	0.2169	likely_benign	0.1915	benign	-0.444	Destabilizing	None	N	0.243	neutral	None	None	None	None	I
A/E	0.2253	likely_benign	0.1947	benign	-0.577	Destabilizing	0.029	N	0.371	neutral	N	0.425093346	None	None	I
A/F	0.2741	likely_benign	0.2574	benign	-0.821	Destabilizing	0.356	N	0.427	neutral	None	None	None	None	I
A/G	0.0993	likely_benign	0.095	benign	-0.37	Destabilizing	None	N	0.09	neutral	N	0.45047458	None	None	I
A/H	0.3924	ambiguous	0.329	benign	-0.263	Destabilizing	0.676	D	0.389	neutral	None	None	None	None	I
A/I	0.175	likely_benign	0.1649	benign	-0.32	Destabilizing	0.12	N	0.431	neutral	None	None	None	None	I
A/K	0.3987	ambiguous	0.3197	benign	-0.664	Destabilizing	0.038	N	0.357	neutral	None	None	None	None	I
A/L	0.1313	likely_benign	0.1178	benign	-0.32	Destabilizing	0.038	N	0.376	neutral	None	None	None	None	I
A/M	0.172	likely_benign	0.1591	benign	-0.478	Destabilizing	0.676	D	0.369	neutral	None	None	None	None	I
A/N	0.15	likely_benign	0.1384	benign	-0.385	Destabilizing	0.038	N	0.447	neutral	None	None	None	None	I
A/P	0.1384	likely_benign	0.1132	benign	-0.282	Destabilizing	None	N	0.188	neutral	N	0.45940187	None	None	I
A/Q	0.276	likely_benign	0.2356	benign	-0.623	Destabilizing	0.214	N	0.425	neutral	None	None	None	None	I
A/R	0.3944	ambiguous	0.3218	benign	-0.189	Destabilizing	0.214	N	0.43	neutral	None	None	None	None	I
A/S	0.0735	likely_benign	0.0751	benign	-0.609	Destabilizing	None	N	0.089	neutral	N	0.416628578	None	None	I
A/T	0.0747	likely_benign	0.0748	benign	-0.656	Destabilizing	None	N	0.089	neutral	N	0.44589548	None	None	I
A/V	0.1069	likely_benign	0.1018	benign	-0.282	Destabilizing	0.029	N	0.254	neutral	N	0.509330883	None	None	I
A/W	0.6043	likely_pathogenic	0.5557	ambiguous	-0.968	Destabilizing	0.864	D	0.467	neutral	None	None	None	None	I
A/Y	0.3761	ambiguous	0.3395	benign	-0.628	Destabilizing	0.356	N	0.416	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.