TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27619	83080;83081;83082	chr2:178563277;178563276;178563275	chr2:179428004;179428003;179428002
N2AB	25978	78157;78158;78159	chr2:178563277;178563276;178563275	chr2:179428004;179428003;179428002
N2A	25051	75376;75377;75378	chr2:178563277;178563276;178563275	chr2:179428004;179428003;179428002
N2B	18554	55885;55886;55887	chr2:178563277;178563276;178563275	chr2:179428004;179428003;179428002
Novex-1	18679	56260;56261;56262	chr2:178563277;178563276;178563275	chr2:179428004;179428003;179428002
Novex-2	18746	56461;56462;56463	chr2:178563277;178563276;178563275	chr2:179428004;179428003;179428002
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-89
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.4942
• 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
T/A	rs1704351645	None	0.334	N	0.366	0.103	0.146414634003	gnomAD-4.0.0	4.77449E-06	None	None	None	None	N	None	0	0	None	0	8.32732E-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
T/A	0.0637	likely_benign	0.0694	benign	-0.583	Destabilizing	0.334	N	0.366	neutral	N	0.468399485	None	None	N
T/C	0.2626	likely_benign	0.3202	benign	-0.292	Destabilizing	0.992	D	0.583	neutral	None	None	None	None	N
T/D	0.4061	ambiguous	0.4658	ambiguous	-0.317	Destabilizing	0.92	D	0.602	neutral	None	None	None	None	N
T/E	0.2623	likely_benign	0.3216	benign	-0.376	Destabilizing	0.617	D	0.564	neutral	None	None	None	None	N
T/F	0.1346	likely_benign	0.1685	benign	-0.924	Destabilizing	0.85	D	0.638	neutral	None	None	None	None	N
T/G	0.2074	likely_benign	0.2463	benign	-0.765	Destabilizing	0.617	D	0.561	neutral	None	None	None	None	N
T/H	0.2287	likely_benign	0.2738	benign	-1.149	Destabilizing	0.977	D	0.595	neutral	None	None	None	None	N
T/I	0.0551	likely_benign	0.0664	benign	-0.21	Destabilizing	0.002	N	0.224	neutral	N	0.43307619	None	None	N
T/K	0.1633	likely_benign	0.1936	benign	-0.635	Destabilizing	0.447	N	0.513	neutral	None	None	None	None	N
T/L	0.0503	likely_benign	0.0585	benign	-0.21	Destabilizing	0.048	N	0.339	neutral	None	None	None	None	N
T/M	0.0647	likely_benign	0.0757	benign	0.2	Stabilizing	0.127	N	0.322	neutral	None	None	None	None	N
T/N	0.1282	likely_benign	0.1498	benign	-0.427	Destabilizing	0.81	D	0.505	neutral	N	0.46489782	None	None	N
T/P	0.0754	likely_benign	0.0797	benign	-0.305	Destabilizing	0.963	D	0.629	neutral	N	0.434980345	None	None	N
T/Q	0.1765	likely_benign	0.2143	benign	-0.721	Destabilizing	0.85	D	0.629	neutral	None	None	None	None	N
T/R	0.132	likely_benign	0.1475	benign	-0.307	Destabilizing	0.005	N	0.303	neutral	None	None	None	None	N
T/S	0.1007	likely_benign	0.1154	benign	-0.629	Destabilizing	0.549	D	0.411	neutral	N	0.472477153	None	None	N
T/V	0.053	likely_benign	0.0642	benign	-0.305	Destabilizing	0.009	N	0.138	neutral	None	None	None	None	N
T/W	0.4749	ambiguous	0.5427	ambiguous	-0.875	Destabilizing	0.992	D	0.615	neutral	None	None	None	None	N
T/Y	0.2052	likely_benign	0.2382	benign	-0.631	Destabilizing	0.92	D	0.622	neutral	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.