TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23326	70201;70202;70203	chr2:178576156;178576155;178576154	chr2:179440883;179440882;179440881
N2AB	21685	65278;65279;65280	chr2:178576156;178576155;178576154	chr2:179440883;179440882;179440881
N2A	20758	62497;62498;62499	chr2:178576156;178576155;178576154	chr2:179440883;179440882;179440881
N2B	14261	43006;43007;43008	chr2:178576156;178576155;178576154	chr2:179440883;179440882;179440881
Novex-1	14386	43381;43382;43383	chr2:178576156;178576155;178576154	chr2:179440883;179440882;179440881
Novex-2	14453	43582;43583;43584	chr2:178576156;178576155;178576154	chr2:179440883;179440882;179440881
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-57
• Domain position: 87
• Structural Position: 119
• Q(SASA): 0.6861
• 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
E/K	None	None	0.958	D	0.667	0.293	0.332133492242	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

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
E/A	0.2802	likely_benign	0.2631	benign	-0.399	Destabilizing	0.958	D	0.717	prob.delet.	N	0.47038128	None	None	I
E/C	0.908	likely_pathogenic	0.8964	pathogenic	-0.109	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
E/D	0.143	likely_benign	0.1415	benign	-0.421	Destabilizing	0.067	N	0.289	neutral	N	0.490564269	None	None	I
E/F	0.8343	likely_pathogenic	0.8082	pathogenic	-0.288	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
E/G	0.3364	likely_benign	0.3273	benign	-0.59	Destabilizing	0.988	D	0.719	prob.delet.	N	0.485180625	None	None	I
E/H	0.6468	likely_pathogenic	0.624	pathogenic	-0.003	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
E/I	0.4494	ambiguous	0.4137	ambiguous	0.068	Stabilizing	0.995	D	0.755	deleterious	None	None	None	None	I
E/K	0.2125	likely_benign	0.2073	benign	0.274	Stabilizing	0.958	D	0.667	neutral	D	0.522905974	None	None	I
E/L	0.4854	ambiguous	0.4429	ambiguous	0.068	Stabilizing	0.995	D	0.748	deleterious	None	None	None	None	I
E/M	0.5414	ambiguous	0.4993	ambiguous	0.123	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
E/N	0.3511	ambiguous	0.3387	benign	-0.049	Destabilizing	0.982	D	0.751	deleterious	None	None	None	None	I
E/P	0.5022	ambiguous	0.5039	ambiguous	-0.068	Destabilizing	0.995	D	0.769	deleterious	None	None	None	None	I
E/Q	0.2008	likely_benign	0.1893	benign	-0.025	Destabilizing	0.994	D	0.723	prob.delet.	N	0.46948268	None	None	I
E/R	0.4036	ambiguous	0.3908	ambiguous	0.509	Stabilizing	0.995	D	0.753	deleterious	None	None	None	None	I
E/S	0.3271	likely_benign	0.3121	benign	-0.203	Destabilizing	0.968	D	0.693	prob.neutral	None	None	None	None	I
E/T	0.3665	ambiguous	0.3404	ambiguous	-0.048	Destabilizing	0.991	D	0.749	deleterious	None	None	None	None	I
E/V	0.3067	likely_benign	0.2763	benign	-0.068	Destabilizing	0.994	D	0.763	deleterious	N	0.483258522	None	None	I
E/W	0.9532	likely_pathogenic	0.9482	pathogenic	-0.136	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	I
E/Y	0.733	likely_pathogenic	0.7119	pathogenic	-0.044	Destabilizing	1.0	D	0.752	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.