TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29933	90022;90023;90024	chr2:178553103;178553102;178553101	chr2:179417830;179417829;179417828
N2AB	28292	85099;85100;85101	chr2:178553103;178553102;178553101	chr2:179417830;179417829;179417828
N2A	27365	82318;82319;82320	chr2:178553103;178553102;178553101	chr2:179417830;179417829;179417828
N2B	20868	62827;62828;62829	chr2:178553103;178553102;178553101	chr2:179417830;179417829;179417828
Novex-1	20993	63202;63203;63204	chr2:178553103;178553102;178553101	chr2:179417830;179417829;179417828
Novex-2	21060	63403;63404;63405	chr2:178553103;178553102;178553101	chr2:179417830;179417829;179417828
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: Fn3-106
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.4354
• 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	0.997	N	0.58	0.263	0.312306559268	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
T/P	rs767264453	-0.526	0.997	N	0.576	0.305	0.298745278005	gnomAD-2.1.1	8.07E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.28E-05	None	0	8.92E-06	0
T/P	rs767264453	-0.526	0.997	N	0.576	0.305	0.298745278005	gnomAD-4.0.0	1.59828E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87533E-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	0.1752	likely_benign	0.1686	benign	-0.677	Destabilizing	0.894	D	0.359	neutral	N	0.471540499	None	None	I
T/C	0.6965	likely_pathogenic	0.6718	pathogenic	-0.356	Destabilizing	1.0	D	0.573	neutral	None	None	None	None	I
T/D	0.8737	likely_pathogenic	0.8319	pathogenic	-0.081	Destabilizing	0.995	D	0.577	neutral	None	None	None	None	I
T/E	0.7151	likely_pathogenic	0.6731	pathogenic	-0.15	Destabilizing	0.995	D	0.572	neutral	None	None	None	None	I
T/F	0.6432	likely_pathogenic	0.5976	pathogenic	-1.102	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	I
T/G	0.5586	ambiguous	0.5137	ambiguous	-0.825	Destabilizing	0.982	D	0.549	neutral	None	None	None	None	I
T/H	0.5705	likely_pathogenic	0.5079	ambiguous	-1.177	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
T/I	0.4089	ambiguous	0.4074	ambiguous	-0.393	Destabilizing	0.997	D	0.58	neutral	N	0.470599136	None	None	I
T/K	0.3831	ambiguous	0.3733	ambiguous	-0.498	Destabilizing	0.993	D	0.569	neutral	N	0.42486406	None	None	I
T/L	0.2812	likely_benign	0.2541	benign	-0.393	Destabilizing	0.991	D	0.601	neutral	None	None	None	None	I
T/M	0.1811	likely_benign	0.1728	benign	0.037	Stabilizing	1.0	D	0.545	neutral	None	None	None	None	I
T/N	0.3725	ambiguous	0.3327	benign	-0.284	Destabilizing	0.995	D	0.581	neutral	None	None	None	None	I
T/P	0.3287	likely_benign	0.3345	benign	-0.459	Destabilizing	0.997	D	0.576	neutral	N	0.47171107	None	None	I
T/Q	0.4669	ambiguous	0.438	ambiguous	-0.609	Destabilizing	0.997	D	0.534	neutral	None	None	None	None	I
T/R	0.3877	ambiguous	0.3665	ambiguous	-0.169	Destabilizing	0.997	D	0.585	neutral	N	0.439390795	None	None	I
T/S	0.1682	likely_benign	0.144	benign	-0.541	Destabilizing	0.615	D	0.129	neutral	N	0.459632781	None	None	I
T/V	0.2832	likely_benign	0.2793	benign	-0.459	Destabilizing	0.991	D	0.588	neutral	None	None	None	None	I
T/W	0.925	likely_pathogenic	0.9043	pathogenic	-1.008	Destabilizing	1.0	D	0.695	prob.delet.	None	None	None	None	I
T/Y	0.6313	likely_pathogenic	0.5857	pathogenic	-0.764	Destabilizing	0.999	D	0.74	deleterious	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.