TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32601	98026;98027;98028	chr2:178540365;178540364;178540363	chr2:179405092;179405091;179405090
N2AB	30960	93103;93104;93105	chr2:178540365;178540364;178540363	chr2:179405092;179405091;179405090
N2A	30033	90322;90323;90324	chr2:178540365;178540364;178540363	chr2:179405092;179405091;179405090
N2B	23536	70831;70832;70833	chr2:178540365;178540364;178540363	chr2:179405092;179405091;179405090
Novex-1	23661	71206;71207;71208	chr2:178540365;178540364;178540363	chr2:179405092;179405091;179405090
Novex-2	23728	71407;71408;71409	chr2:178540365;178540364;178540363	chr2:179405092;179405091;179405090
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: Fn3-126
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.1675
• 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	rs745324961	-0.109	1.0	D	0.856	0.485	0.815470345074	gnomAD-2.1.1	8.13E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.8E-05	0
P/L	rs745324961	-0.109	1.0	D	0.856	0.485	0.815470345074	gnomAD-4.0.0	3.19649E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.74257E-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	0.6457	likely_pathogenic	0.7174	pathogenic	-1.168	Destabilizing	0.999	D	0.811	deleterious	D	0.548694692	None	None	N
P/C	0.9549	likely_pathogenic	0.9655	pathogenic	-1.935	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
P/D	0.9985	likely_pathogenic	0.999	pathogenic	-3.144	Highly Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
P/E	0.9953	likely_pathogenic	0.9969	pathogenic	-3.107	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
P/F	0.9981	likely_pathogenic	0.9989	pathogenic	-1.002	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
P/G	0.9791	likely_pathogenic	0.9864	pathogenic	-1.45	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
P/H	0.993	likely_pathogenic	0.9954	pathogenic	-0.935	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
P/I	0.9771	likely_pathogenic	0.9837	pathogenic	-0.463	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
P/K	0.9959	likely_pathogenic	0.9975	pathogenic	-1.304	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
P/L	0.9253	likely_pathogenic	0.9444	pathogenic	-0.463	Destabilizing	1.0	D	0.856	deleterious	D	0.530083458	None	None	N
P/M	0.9897	likely_pathogenic	0.9928	pathogenic	-0.762	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
P/N	0.998	likely_pathogenic	0.9986	pathogenic	-1.649	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
P/Q	0.9894	likely_pathogenic	0.9931	pathogenic	-1.857	Destabilizing	1.0	D	0.843	deleterious	D	0.56122954	None	None	N
P/R	0.9825	likely_pathogenic	0.9882	pathogenic	-0.841	Destabilizing	1.0	D	0.836	deleterious	D	0.560722561	None	None	N
P/S	0.9503	likely_pathogenic	0.9661	pathogenic	-1.911	Destabilizing	1.0	D	0.79	deleterious	N	0.518980642	None	None	N
P/T	0.9407	likely_pathogenic	0.9565	pathogenic	-1.775	Destabilizing	1.0	D	0.799	deleterious	D	0.534224515	None	None	N
P/V	0.9235	likely_pathogenic	0.9413	pathogenic	-0.67	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
P/W	0.9991	likely_pathogenic	0.9995	pathogenic	-1.324	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
P/Y	0.9982	likely_pathogenic	0.9989	pathogenic	-0.928	Destabilizing	1.0	D	0.837	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.