TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5480	16663;16664;16665	chr2:178732623;178732622;178732621	chr2:179597350;179597349;179597348
N2AB	5163	15712;15713;15714	chr2:178732623;178732622;178732621	chr2:179597350;179597349;179597348
N2A	4236	12931;12932;12933	chr2:178732623;178732622;178732621	chr2:179597350;179597349;179597348
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-38
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.4266
• 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/K	rs753485630	-0.304	0.006	N	0.235	0.322	0.373173300195	gnomAD-2.1.1	4.84E-05	None	None	None	None	I	None	0	0	None	0	6.16385E-04	None	0	None	0	8.92E-06	0
T/K	rs753485630	-0.304	0.006	N	0.235	0.322	0.373173300195	gnomAD-4.0.0	1.27344E-05	None	None	None	None	I	None	0	0	None	0	1.66713E-04	None	0	0	2.85871E-06	0	3.02535E-05
T/R	None	None	0.473	N	0.541	0.328	0.487208542674	gnomAD-4.0.0	1.59179E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85871E-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	0.0809	likely_benign	0.0808	benign	-0.571	Destabilizing	0.01	N	0.105	neutral	N	0.503101997	None	None	I
T/C	0.4357	ambiguous	0.4481	ambiguous	-0.384	Destabilizing	0.995	D	0.495	neutral	None	None	None	None	I
T/D	0.261	likely_benign	0.2932	benign	0.123	Stabilizing	0.543	D	0.487	neutral	None	None	None	None	I
T/E	0.2104	likely_benign	0.2461	benign	0.097	Stabilizing	0.543	D	0.473	neutral	None	None	None	None	I
T/F	0.1935	likely_benign	0.2148	benign	-0.791	Destabilizing	0.893	D	0.565	neutral	None	None	None	None	I
T/G	0.2441	likely_benign	0.2477	benign	-0.789	Destabilizing	0.329	N	0.43	neutral	None	None	None	None	I
T/H	0.1818	likely_benign	0.1922	benign	-1.077	Destabilizing	0.944	D	0.551	neutral	None	None	None	None	I
T/I	0.1373	likely_benign	0.159	benign	-0.097	Destabilizing	0.473	N	0.538	neutral	D	0.534502339	None	None	I
T/K	0.1728	likely_benign	0.1872	benign	-0.572	Destabilizing	0.006	N	0.235	neutral	N	0.446939283	None	None	I
T/L	0.0961	likely_benign	0.1063	benign	-0.097	Destabilizing	0.329	N	0.424	neutral	None	None	None	None	I
T/M	0.0871	likely_benign	0.095	benign	0.047	Stabilizing	0.176	N	0.304	neutral	None	None	None	None	I
T/N	0.0982	likely_benign	0.0997	benign	-0.435	Destabilizing	0.031	N	0.277	neutral	None	None	None	None	I
T/P	0.3338	likely_benign	0.353	ambiguous	-0.223	Destabilizing	0.784	D	0.565	neutral	N	0.500571489	None	None	I
T/Q	0.1673	likely_benign	0.1801	benign	-0.582	Destabilizing	0.893	D	0.565	neutral	None	None	None	None	I
T/R	0.1415	likely_benign	0.1511	benign	-0.362	Destabilizing	0.473	N	0.541	neutral	N	0.482630724	None	None	I
T/S	0.094	likely_benign	0.0936	benign	-0.695	Destabilizing	0.023	N	0.131	neutral	N	0.446264492	None	None	I
T/V	0.1154	likely_benign	0.1275	benign	-0.223	Destabilizing	0.329	N	0.358	neutral	None	None	None	None	I
T/W	0.4809	ambiguous	0.5254	ambiguous	-0.766	Destabilizing	0.995	D	0.575	neutral	None	None	None	None	I
T/Y	0.2176	likely_benign	0.2345	benign	-0.509	Destabilizing	0.981	D	0.571	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.