TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8647	26164;26165;26166	chr2:178715247;178715246;178715245	chr2:179579974;179579973;179579972
N2AB	8330	25213;25214;25215	chr2:178715247;178715246;178715245	chr2:179579974;179579973;179579972
N2A	7403	22432;22433;22434	chr2:178715247;178715246;178715245	chr2:179579974;179579973;179579972
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-72
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.5943
• 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
K/R	None	None	0.001	N	0.209	0.078	0.243972157842	gnomAD-4.0.0	1.37709E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.80549E-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
K/A	0.3569	ambiguous	0.3608	ambiguous	-0.492	Destabilizing	0.546	D	0.487	neutral	None	None	None	None	I
K/C	0.6166	likely_pathogenic	0.6339	pathogenic	-0.248	Destabilizing	0.99	D	0.619	neutral	None	None	None	None	I
K/D	0.536	ambiguous	0.5384	ambiguous	-0.327	Destabilizing	0.376	N	0.483	neutral	None	None	None	None	I
K/E	0.1584	likely_benign	0.1556	benign	-0.206	Destabilizing	0.12	N	0.48	neutral	D	0.52376527	None	None	I
K/F	0.6939	likely_pathogenic	0.6959	pathogenic	0.073	Stabilizing	0.773	D	0.584	neutral	None	None	None	None	I
K/G	0.3928	ambiguous	0.3844	ambiguous	-0.883	Destabilizing	0.376	N	0.521	neutral	None	None	None	None	I
K/H	0.2767	likely_benign	0.2801	benign	-1.292	Destabilizing	0.004	N	0.362	neutral	None	None	None	None	I
K/I	0.2943	likely_benign	0.3143	benign	0.539	Stabilizing	0.16	N	0.584	neutral	N	0.512798915	None	None	I
K/L	0.2932	likely_benign	0.3138	benign	0.539	Stabilizing	0.034	N	0.509	neutral	None	None	None	None	I
K/M	0.2168	likely_benign	0.2275	benign	0.38	Stabilizing	0.921	D	0.511	neutral	None	None	None	None	I
K/N	0.3403	ambiguous	0.3277	benign	-0.477	Destabilizing	0.003	N	0.209	neutral	N	0.512510914	None	None	I
K/P	0.8604	likely_pathogenic	0.8631	pathogenic	0.225	Stabilizing	0.895	D	0.493	neutral	None	None	None	None	I
K/Q	0.1103	likely_benign	0.1103	benign	-0.454	Destabilizing	0.278	N	0.443	neutral	N	0.491439421	None	None	I
K/R	0.0735	likely_benign	0.0775	benign	-0.88	Destabilizing	0.001	N	0.209	neutral	N	0.474029883	None	None	I
K/S	0.3562	ambiguous	0.3556	ambiguous	-0.97	Destabilizing	0.376	N	0.434	neutral	None	None	None	None	I
K/T	0.1801	likely_benign	0.1802	benign	-0.656	Destabilizing	0.214	N	0.479	neutral	N	0.515799148	None	None	I
K/V	0.2777	likely_benign	0.2946	benign	0.225	Stabilizing	0.14	N	0.537	neutral	None	None	None	None	I
K/W	0.6316	likely_pathogenic	0.644	pathogenic	0.116	Stabilizing	0.993	D	0.649	neutral	None	None	None	None	I
K/Y	0.5388	ambiguous	0.5432	ambiguous	0.339	Stabilizing	0.09	N	0.575	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.