TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24040	72343;72344;72345	chr2:178574014;178574013;178574012	chr2:179438741;179438740;179438739
N2AB	22399	67420;67421;67422	chr2:178574014;178574013;178574012	chr2:179438741;179438740;179438739
N2A	21472	64639;64640;64641	chr2:178574014;178574013;178574012	chr2:179438741;179438740;179438739
N2B	14975	45148;45149;45150	chr2:178574014;178574013;178574012	chr2:179438741;179438740;179438739
Novex-1	15100	45523;45524;45525	chr2:178574014;178574013;178574012	chr2:179438741;179438740;179438739
Novex-2	15167	45724;45725;45726	chr2:178574014;178574013;178574012	chr2:179438741;179438740;179438739
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-131
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.3117
• 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
I/L	None	None	0.002	N	0.224	0.115	0.405012372841	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
I/T	None	None	None	N	0.163	0.126	0.270889551736	gnomAD-4.0.0	1.36874E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79916E-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
I/A	0.2428	likely_benign	0.295	benign	-0.998	Destabilizing	0.007	N	0.268	neutral	None	None	None	None	I
I/C	0.4971	ambiguous	0.5574	ambiguous	-0.814	Destabilizing	0.356	N	0.305	neutral	None	None	None	None	I
I/D	0.5532	ambiguous	0.6236	pathogenic	-0.175	Destabilizing	0.072	N	0.414	neutral	None	None	None	None	I
I/E	0.4268	ambiguous	0.4692	ambiguous	-0.202	Destabilizing	0.072	N	0.416	neutral	None	None	None	None	I
I/F	0.1201	likely_benign	0.1372	benign	-0.634	Destabilizing	0.072	N	0.273	neutral	None	None	None	None	I
I/G	0.5197	ambiguous	0.6033	pathogenic	-1.253	Destabilizing	0.072	N	0.397	neutral	None	None	None	None	I
I/H	0.3383	likely_benign	0.3643	ambiguous	-0.381	Destabilizing	0.864	D	0.341	neutral	None	None	None	None	I
I/K	0.3069	likely_benign	0.3251	benign	-0.648	Destabilizing	0.055	N	0.439	neutral	N	0.459289717	None	None	I
I/L	0.0809	likely_benign	0.0883	benign	-0.411	Destabilizing	0.002	N	0.224	neutral	N	0.458329712	None	None	I
I/M	0.0938	likely_benign	0.1026	benign	-0.487	Destabilizing	0.295	N	0.282	neutral	N	0.48632439	None	None	I
I/N	0.1882	likely_benign	0.2105	benign	-0.538	Destabilizing	0.214	N	0.429	neutral	None	None	None	None	I
I/P	0.5818	likely_pathogenic	0.6619	pathogenic	-0.573	Destabilizing	0.356	N	0.429	neutral	None	None	None	None	I
I/Q	0.3057	likely_benign	0.3256	benign	-0.675	Destabilizing	0.356	N	0.373	neutral	None	None	None	None	I
I/R	0.2398	likely_benign	0.2573	benign	-0.118	Destabilizing	0.171	N	0.407	neutral	N	0.441109388	None	None	I
I/S	0.1902	likely_benign	0.219	benign	-1.118	Destabilizing	0.016	N	0.317	neutral	None	None	None	None	I
I/T	0.105	likely_benign	0.1239	benign	-1.025	Destabilizing	None	N	0.163	neutral	N	0.395625028	None	None	I
I/V	0.0643	likely_benign	0.0691	benign	-0.573	Destabilizing	None	N	0.133	neutral	N	0.36809171	None	None	I
I/W	0.6682	likely_pathogenic	0.717	pathogenic	-0.672	Destabilizing	0.864	D	0.356	neutral	None	None	None	None	I
I/Y	0.3682	ambiguous	0.3797	ambiguous	-0.442	Destabilizing	0.356	N	0.346	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.