TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29079	87460;87461;87462	chr2:178558119;178558118;178558117	chr2:179422846;179422845;179422844
N2AB	27438	82537;82538;82539	chr2:178558119;178558118;178558117	chr2:179422846;179422845;179422844
N2A	26511	79756;79757;79758	chr2:178558119;178558118;178558117	chr2:179422846;179422845;179422844
N2B	20014	60265;60266;60267	chr2:178558119;178558118;178558117	chr2:179422846;179422845;179422844
Novex-1	20139	60640;60641;60642	chr2:178558119;178558118;178558117	chr2:179422846;179422845;179422844
Novex-2	20206	60841;60842;60843	chr2:178558119;178558118;178558117	chr2:179422846;179422845;179422844
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-145
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.1508
• 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
S/P	rs1702220233	None	1.0	N	0.838	0.511	0.26547132957	gnomAD-4.0.0	1.5911E-06	None	None	None	None	N	None	0	0	None	0	2.77362E-05	None	0	0	0	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	0.0857	likely_benign	0.0866	benign	-0.96	Destabilizing	0.997	D	0.547	neutral	N	0.450639231	None	None	N
S/C	0.0788	likely_benign	0.0824	benign	-0.876	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
S/D	0.4898	ambiguous	0.5133	ambiguous	-0.883	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
S/E	0.51	ambiguous	0.5202	ambiguous	-0.807	Destabilizing	0.999	D	0.678	prob.neutral	None	None	None	None	N
S/F	0.1217	likely_benign	0.1234	benign	-1.058	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
S/G	0.1193	likely_benign	0.1346	benign	-1.262	Destabilizing	0.999	D	0.615	neutral	None	None	None	None	N
S/H	0.2762	likely_benign	0.2792	benign	-1.677	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
S/I	0.1301	likely_benign	0.142	benign	-0.239	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
S/K	0.6096	likely_pathogenic	0.6595	pathogenic	-0.657	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
S/L	0.0684	likely_benign	0.0709	benign	-0.239	Destabilizing	1.0	D	0.798	deleterious	N	0.459995354	None	None	N
S/M	0.1345	likely_benign	0.1445	benign	-0.062	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
S/N	0.1493	likely_benign	0.172	benign	-0.937	Destabilizing	0.999	D	0.672	neutral	None	None	None	None	N
S/P	0.9129	likely_pathogenic	0.9365	pathogenic	-0.446	Destabilizing	1.0	D	0.838	deleterious	N	0.462920589	None	None	N
S/Q	0.4105	ambiguous	0.4233	ambiguous	-0.999	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
S/R	0.5345	ambiguous	0.582	pathogenic	-0.693	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
S/T	0.0695	likely_benign	0.0765	benign	-0.845	Destabilizing	0.999	D	0.569	neutral	N	0.46344109	None	None	N
S/V	0.1369	likely_benign	0.1422	benign	-0.446	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
S/W	0.2553	likely_benign	0.2425	benign	-1.068	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
S/Y	0.1439	likely_benign	0.1443	benign	-0.746	Destabilizing	1.0	D	0.851	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.