TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17039	51340;51341;51342	chr2:178611014;178611013;178611012	chr2:179475741;179475740;179475739
N2AB	15398	46417;46418;46419	chr2:178611014;178611013;178611012	chr2:179475741;179475740;179475739
N2A	14471	43636;43637;43638	chr2:178611014;178611013;178611012	chr2:179475741;179475740;179475739
N2B	7974	24145;24146;24147	chr2:178611014;178611013;178611012	chr2:179475741;179475740;179475739
Novex-1	8099	24520;24521;24522	chr2:178611014;178611013;178611012	chr2:179475741;179475740;179475739
Novex-2	8166	24721;24722;24723	chr2:178611014;178611013;178611012	chr2:179475741;179475740;179475739
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-111
• Domain position: 85
• Structural Position: 171
• Q(SASA): 0.3146
• 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/T	None	None	0.007	N	0.177	0.105	0.257786959452	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.0831	likely_benign	0.0873	benign	-0.518	Destabilizing	0.022	N	0.177	neutral	N	0.513755328	None	None	N
S/C	0.1463	likely_benign	0.145	benign	-0.272	Destabilizing	0.998	D	0.569	neutral	None	None	None	None	N
S/D	0.3649	ambiguous	0.3637	ambiguous	0.075	Stabilizing	0.842	D	0.499	neutral	None	None	None	None	N
S/E	0.412	ambiguous	0.4186	ambiguous	0.037	Stabilizing	0.842	D	0.497	neutral	None	None	None	None	N
S/F	0.2269	likely_benign	0.2426	benign	-0.859	Destabilizing	0.974	D	0.659	neutral	None	None	None	None	N
S/G	0.1161	likely_benign	0.1115	benign	-0.726	Destabilizing	0.688	D	0.503	neutral	None	None	None	None	N
S/H	0.3034	likely_benign	0.3083	benign	-1.259	Destabilizing	0.998	D	0.569	neutral	None	None	None	None	N
S/I	0.1737	likely_benign	0.1921	benign	-0.086	Destabilizing	0.949	D	0.664	neutral	None	None	None	None	N
S/K	0.4729	ambiguous	0.5066	ambiguous	-0.582	Destabilizing	0.842	D	0.487	neutral	None	None	None	None	N
S/L	0.1231	likely_benign	0.1336	benign	-0.086	Destabilizing	0.669	D	0.591	neutral	D	0.600701041	None	None	N
S/M	0.1982	likely_benign	0.2094	benign	0.155	Stabilizing	0.991	D	0.578	neutral	None	None	None	None	N
S/N	0.1193	likely_benign	0.1194	benign	-0.393	Destabilizing	0.842	D	0.517	neutral	None	None	None	None	N
S/P	0.3272	likely_benign	0.3164	benign	-0.196	Destabilizing	0.966	D	0.589	neutral	D	0.536119677	None	None	N
S/Q	0.3933	ambiguous	0.4098	ambiguous	-0.544	Destabilizing	0.974	D	0.566	neutral	None	None	None	None	N
S/R	0.4359	ambiguous	0.4576	ambiguous	-0.482	Destabilizing	0.949	D	0.598	neutral	None	None	None	None	N
S/T	0.0665	likely_benign	0.0696	benign	-0.431	Destabilizing	0.007	N	0.177	neutral	N	0.439426116	None	None	N
S/V	0.1685	likely_benign	0.1847	benign	-0.196	Destabilizing	0.728	D	0.592	neutral	None	None	None	None	N
S/W	0.4159	ambiguous	0.42	ambiguous	-0.868	Destabilizing	0.998	D	0.679	prob.neutral	None	None	None	None	N
S/Y	0.2087	likely_benign	0.2195	benign	-0.594	Destabilizing	0.991	D	0.651	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.