TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21960	66103;66104;66105	chr2:178582578;178582577;178582576	chr2:179447305;179447304;179447303
N2AB	20319	61180;61181;61182	chr2:178582578;178582577;178582576	chr2:179447305;179447304;179447303
N2A	19392	58399;58400;58401	chr2:178582578;178582577;178582576	chr2:179447305;179447304;179447303
N2B	12895	38908;38909;38910	chr2:178582578;178582577;178582576	chr2:179447305;179447304;179447303
Novex-1	13020	39283;39284;39285	chr2:178582578;178582577;178582576	chr2:179447305;179447304;179447303
Novex-2	13087	39484;39485;39486	chr2:178582578;178582577;178582576	chr2:179447305;179447304;179447303
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-47
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.1102
• 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
P/L	None	None	0.025	D	0.775	0.576	0.589785090976	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31252E-06	0	0
P/T	None	None	0.967	D	0.827	0.624	0.543299242062	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31252E-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
P/A	0.6642	likely_pathogenic	0.5177	ambiguous	-2.05	Highly Destabilizing	0.805	D	0.785	deleterious	D	0.527192255	None	None	N
P/C	0.895	likely_pathogenic	0.8495	pathogenic	-1.707	Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
P/D	0.9994	likely_pathogenic	0.9989	pathogenic	-3.231	Highly Destabilizing	0.996	D	0.833	deleterious	None	None	None	None	N
P/E	0.9975	likely_pathogenic	0.9959	pathogenic	-2.949	Highly Destabilizing	0.987	D	0.839	deleterious	None	None	None	None	N
P/F	0.999	likely_pathogenic	0.9979	pathogenic	-1.017	Destabilizing	0.975	D	0.901	deleterious	None	None	None	None	N
P/G	0.9915	likely_pathogenic	0.9843	pathogenic	-2.62	Highly Destabilizing	0.987	D	0.858	deleterious	None	None	None	None	N
P/H	0.9984	likely_pathogenic	0.9967	pathogenic	-2.582	Highly Destabilizing	0.999	D	0.862	deleterious	None	None	None	None	N
P/I	0.8447	likely_pathogenic	0.772	pathogenic	-0.411	Destabilizing	0.845	D	0.883	deleterious	None	None	None	None	N
P/K	0.9989	likely_pathogenic	0.9981	pathogenic	-1.681	Destabilizing	0.987	D	0.825	deleterious	None	None	None	None	N
P/L	0.9108	likely_pathogenic	0.8278	pathogenic	-0.411	Destabilizing	0.025	N	0.775	deleterious	D	0.555892347	None	None	N
P/M	0.9772	likely_pathogenic	0.9562	pathogenic	-0.752	Destabilizing	0.993	D	0.883	deleterious	None	None	None	None	N
P/N	0.9985	likely_pathogenic	0.9971	pathogenic	-2.247	Highly Destabilizing	0.996	D	0.873	deleterious	None	None	None	None	N
P/Q	0.996	likely_pathogenic	0.9924	pathogenic	-1.954	Destabilizing	0.994	D	0.808	deleterious	D	0.569023079	None	None	N
P/R	0.9968	likely_pathogenic	0.994	pathogenic	-1.723	Destabilizing	0.983	D	0.873	deleterious	D	0.5685161	None	None	N
P/S	0.9724	likely_pathogenic	0.9418	pathogenic	-2.736	Highly Destabilizing	0.983	D	0.821	deleterious	D	0.557413284	None	None	N
P/T	0.8846	likely_pathogenic	0.8039	pathogenic	-2.312	Highly Destabilizing	0.967	D	0.827	deleterious	D	0.556652816	None	None	N
P/V	0.4954	ambiguous	0.4257	ambiguous	-0.937	Destabilizing	0.073	N	0.74	deleterious	None	None	None	None	N
P/W	0.9999	likely_pathogenic	0.9998	pathogenic	-1.693	Destabilizing	0.999	D	0.854	deleterious	None	None	None	None	N
P/Y	0.9997	likely_pathogenic	0.9993	pathogenic	-1.314	Destabilizing	0.987	D	0.91	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.