TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20147	60664;60665;60666	chr2:178591286;178591285;178591284	chr2:179456013;179456012;179456011
N2AB	18506	55741;55742;55743	chr2:178591286;178591285;178591284	chr2:179456013;179456012;179456011
N2A	17579	52960;52961;52962	chr2:178591286;178591285;178591284	chr2:179456013;179456012;179456011
N2B	11082	33469;33470;33471	chr2:178591286;178591285;178591284	chr2:179456013;179456012;179456011
Novex-1	11207	33844;33845;33846	chr2:178591286;178591285;178591284	chr2:179456013;179456012;179456011
Novex-2	11274	34045;34046;34047	chr2:178591286;178591285;178591284	chr2:179456013;179456012;179456011
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-120
• Domain position: 68
• Structural Position: 152
• Q(SASA): 0.1776
• 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
G/E	rs754537684	-1.384	1.0	D	0.839	0.678	0.836966666681	gnomAD-2.1.1	2.42E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.96528E-04	None	0	0	0
G/E	rs754537684	-1.384	1.0	D	0.839	0.678	0.836966666681	gnomAD-4.0.0	8.21335E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.27643E-04	1.65711E-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
G/A	0.2926	likely_benign	0.2905	benign	-0.677	Destabilizing	1.0	D	0.737	prob.delet.	D	0.557057218	None	None	N
G/C	0.6285	likely_pathogenic	0.6232	pathogenic	-0.932	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
G/D	0.7739	likely_pathogenic	0.7705	pathogenic	-1.051	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
G/E	0.8001	likely_pathogenic	0.7963	pathogenic	-1.12	Destabilizing	1.0	D	0.839	deleterious	D	0.642533094	None	None	N
G/F	0.9577	likely_pathogenic	0.9578	pathogenic	-1.071	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
G/H	0.862	likely_pathogenic	0.8543	pathogenic	-1.268	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
G/I	0.9368	likely_pathogenic	0.9372	pathogenic	-0.325	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
G/K	0.7672	likely_pathogenic	0.7704	pathogenic	-1.162	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
G/L	0.8827	likely_pathogenic	0.8784	pathogenic	-0.325	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
G/M	0.8913	likely_pathogenic	0.8886	pathogenic	-0.284	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
G/N	0.7743	likely_pathogenic	0.7551	pathogenic	-0.822	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
G/P	0.9971	likely_pathogenic	0.9971	pathogenic	-0.401	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
G/Q	0.717	likely_pathogenic	0.708	pathogenic	-1.015	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
G/R	0.6344	likely_pathogenic	0.6372	pathogenic	-0.842	Destabilizing	1.0	D	0.831	deleterious	D	0.64233129	None	None	N
G/S	0.2825	likely_benign	0.2638	benign	-1.088	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
G/T	0.6491	likely_pathogenic	0.6388	pathogenic	-1.071	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
G/V	0.8405	likely_pathogenic	0.8441	pathogenic	-0.401	Destabilizing	1.0	D	0.817	deleterious	D	0.642533094	None	None	N
G/W	0.9339	likely_pathogenic	0.9321	pathogenic	-1.403	Destabilizing	1.0	D	0.781	deleterious	D	0.642734898	None	None	N
G/Y	0.935	likely_pathogenic	0.9366	pathogenic	-0.985	Destabilizing	1.0	D	0.785	deleterious	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.