TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33578	100957;100958;100959	chr2:178536015;178536014;178536013	chr2:179400742;179400741;179400740
N2AB	31937	96034;96035;96036	chr2:178536015;178536014;178536013	chr2:179400742;179400741;179400740
N2A	31010	93253;93254;93255	chr2:178536015;178536014;178536013	chr2:179400742;179400741;179400740
N2B	24513	73762;73763;73764	chr2:178536015;178536014;178536013	chr2:179400742;179400741;179400740
Novex-1	24638	74137;74138;74139	chr2:178536015;178536014;178536013	chr2:179400742;179400741;179400740
Novex-2	24705	74338;74339;74340	chr2:178536015;178536014;178536013	chr2:179400742;179400741;179400740
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-158
• Domain position: 83
• Structural Position: 165
• Q(SASA): 0.3819
• 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
S/P	rs749424660	-0.53	0.999	N	0.719	0.612	None	gnomAD-2.1.1	9.69E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	2.06E-05	0
S/P	rs749424660	-0.53	0.999	N	0.719	0.612	None	gnomAD-4.0.0	5.25819E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.31544E-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
S/A	0.1122	likely_benign	0.1099	benign	-0.572	Destabilizing	0.936	D	0.503	neutral	N	0.494386513	None	None	I
S/C	0.2774	likely_benign	0.264	benign	-0.408	Destabilizing	1.0	D	0.712	prob.delet.	N	0.501585447	None	None	I
S/D	0.9393	likely_pathogenic	0.9189	pathogenic	-0.14	Destabilizing	0.998	D	0.66	neutral	None	None	None	None	I
S/E	0.9306	likely_pathogenic	0.9105	pathogenic	-0.231	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	I
S/F	0.5988	likely_pathogenic	0.5408	ambiguous	-1.094	Destabilizing	1.0	D	0.767	deleterious	D	0.53769736	None	None	I
S/G	0.3574	ambiguous	0.3129	benign	-0.694	Destabilizing	0.999	D	0.535	neutral	None	None	None	None	I
S/H	0.8436	likely_pathogenic	0.8015	pathogenic	-1.213	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
S/I	0.5237	ambiguous	0.4723	ambiguous	-0.373	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
S/K	0.983	likely_pathogenic	0.9766	pathogenic	-0.651	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	I
S/L	0.3413	ambiguous	0.3193	benign	-0.373	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	I
S/M	0.4285	ambiguous	0.4187	ambiguous	0.019	Stabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	I
S/N	0.5447	ambiguous	0.4873	ambiguous	-0.381	Destabilizing	0.987	D	0.646	neutral	None	None	None	None	I
S/P	0.953	likely_pathogenic	0.9166	pathogenic	-0.412	Destabilizing	0.999	D	0.719	prob.delet.	N	0.512688263	None	None	I
S/Q	0.879	likely_pathogenic	0.8432	pathogenic	-0.708	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
S/R	0.9694	likely_pathogenic	0.9557	pathogenic	-0.379	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
S/T	0.1964	likely_benign	0.1737	benign	-0.507	Destabilizing	0.982	D	0.528	neutral	N	0.488095259	None	None	I
S/V	0.4386	ambiguous	0.4091	ambiguous	-0.412	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
S/W	0.8568	likely_pathogenic	0.8105	pathogenic	-1.034	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	I
S/Y	0.6336	likely_pathogenic	0.5915	pathogenic	-0.792	Destabilizing	1.0	D	0.762	deleterious	N	0.488000642	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.