TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8657	26194;26195;26196	chr2:178715217;178715216;178715215	chr2:179579944;179579943;179579942
N2AB	8340	25243;25244;25245	chr2:178715217;178715216;178715215	chr2:179579944;179579943;179579942
N2A	7413	22462;22463;22464	chr2:178715217;178715216;178715215	chr2:179579944;179579943;179579942
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: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-72
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.344
• 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/A	rs766866317	None	0.72	D	0.632	0.741	0.428747304603	gnomAD-4.0.0	4.8013E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25002E-06	0	0
G/E	rs766866317	None	0.99	D	0.735	0.781	None	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
G/A	0.2341	likely_benign	0.2486	benign	-0.451	Destabilizing	0.72	D	0.632	neutral	D	0.639380999	None	None	N
G/C	0.4844	ambiguous	0.5028	ambiguous	-0.863	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
G/D	0.2832	likely_benign	0.2703	benign	-0.984	Destabilizing	0.962	D	0.752	deleterious	None	None	None	None	N
G/E	0.3742	ambiguous	0.3655	ambiguous	-1.152	Destabilizing	0.99	D	0.735	prob.delet.	D	0.575283913	None	None	N
G/F	0.7067	likely_pathogenic	0.7459	pathogenic	-1.204	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
G/H	0.5769	likely_pathogenic	0.5894	pathogenic	-0.714	Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
G/I	0.5881	likely_pathogenic	0.614	pathogenic	-0.552	Destabilizing	0.996	D	0.765	deleterious	None	None	None	None	N
G/K	0.6957	likely_pathogenic	0.7126	pathogenic	-0.982	Destabilizing	0.986	D	0.733	prob.delet.	None	None	None	None	N
G/L	0.6278	likely_pathogenic	0.6546	pathogenic	-0.552	Destabilizing	0.993	D	0.73	prob.delet.	None	None	None	None	N
G/M	0.6145	likely_pathogenic	0.6449	pathogenic	-0.39	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
G/N	0.276	likely_benign	0.2723	benign	-0.595	Destabilizing	0.22	N	0.453	neutral	None	None	None	None	N
G/P	0.9551	likely_pathogenic	0.9617	pathogenic	-0.485	Destabilizing	0.99	D	0.769	deleterious	None	None	None	None	N
G/Q	0.5464	ambiguous	0.5538	ambiguous	-0.944	Destabilizing	0.993	D	0.769	deleterious	None	None	None	None	N
G/R	0.5992	likely_pathogenic	0.6099	pathogenic	-0.443	Destabilizing	0.99	D	0.767	deleterious	D	0.618223655	None	None	N
G/S	0.1524	likely_benign	0.1551	benign	-0.711	Destabilizing	0.174	N	0.427	neutral	None	None	None	None	N
G/T	0.2937	likely_benign	0.3094	benign	-0.821	Destabilizing	0.986	D	0.715	prob.delet.	None	None	None	None	N
G/V	0.4209	ambiguous	0.4483	ambiguous	-0.485	Destabilizing	0.99	D	0.741	deleterious	D	0.655803968	None	None	N
G/W	0.5813	likely_pathogenic	0.6043	pathogenic	-1.346	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
G/Y	0.5196	ambiguous	0.5437	ambiguous	-1.009	Destabilizing	1.0	D	0.778	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.