TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22423	67492;67493;67494	chr2:178580020;178580019;178580018	chr2:179444747;179444746;179444745
N2AB	20782	62569;62570;62571	chr2:178580020;178580019;178580018	chr2:179444747;179444746;179444745
N2A	19855	59788;59789;59790	chr2:178580020;178580019;178580018	chr2:179444747;179444746;179444745
N2B	13358	40297;40298;40299	chr2:178580020;178580019;178580018	chr2:179444747;179444746;179444745
Novex-1	13483	40672;40673;40674	chr2:178580020;178580019;178580018	chr2:179444747;179444746;179444745
Novex-2	13550	40873;40874;40875	chr2:178580020;178580019;178580018	chr2:179444747;179444746;179444745
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Fn3-50
• Domain position: 70
• Structural Position: 103
• Q(SASA): 0.214
• 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/C	None	None	0.994	N	0.479	0.445	0.41337360676	gnomAD-4.0.0	8.40235E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.18763E-06	0	0
S/P	None	None	0.007	N	0.229	0.193	0.126345400529	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31252E-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	0.0878	likely_benign	0.0819	benign	-0.72	Destabilizing	0.012	N	0.154	neutral	N	0.494372578	None	None	N
S/C	0.0881	likely_benign	0.0804	benign	-0.417	Destabilizing	0.994	D	0.479	neutral	N	0.487866878	None	None	N
S/D	0.5539	ambiguous	0.5177	ambiguous	-0.536	Destabilizing	0.854	D	0.42	neutral	None	None	None	None	N
S/E	0.5802	likely_pathogenic	0.5384	ambiguous	-0.452	Destabilizing	0.742	D	0.411	neutral	None	None	None	None	N
S/F	0.2605	likely_benign	0.2436	benign	-0.57	Destabilizing	0.979	D	0.601	neutral	N	0.46801465	None	None	N
S/G	0.1245	likely_benign	0.1166	benign	-1.062	Destabilizing	0.373	N	0.404	neutral	None	None	None	None	N
S/H	0.414	ambiguous	0.3806	ambiguous	-1.444	Destabilizing	0.996	D	0.483	neutral	None	None	None	None	N
S/I	0.1784	likely_benign	0.1713	benign	0.107	Stabilizing	0.953	D	0.558	neutral	None	None	None	None	N
S/K	0.7544	likely_pathogenic	0.7254	pathogenic	-0.581	Destabilizing	0.742	D	0.399	neutral	None	None	None	None	N
S/L	0.1099	likely_benign	0.1027	benign	0.107	Stabilizing	0.742	D	0.509	neutral	None	None	None	None	N
S/M	0.2011	likely_benign	0.1835	benign	0.245	Stabilizing	0.996	D	0.489	neutral	None	None	None	None	N
S/N	0.1493	likely_benign	0.1371	benign	-0.782	Destabilizing	0.854	D	0.455	neutral	None	None	None	None	N
S/P	0.2136	likely_benign	0.2198	benign	-0.132	Destabilizing	0.007	N	0.229	neutral	N	0.490236195	None	None	N
S/Q	0.5339	ambiguous	0.4932	ambiguous	-0.751	Destabilizing	0.953	D	0.453	neutral	None	None	None	None	N
S/R	0.6878	likely_pathogenic	0.6624	pathogenic	-0.683	Destabilizing	0.953	D	0.48	neutral	None	None	None	None	N
S/T	0.0984	likely_benign	0.0927	benign	-0.677	Destabilizing	0.472	N	0.449	neutral	N	0.447349422	None	None	N
S/V	0.1801	likely_benign	0.1669	benign	-0.132	Destabilizing	0.742	D	0.497	neutral	None	None	None	None	N
S/W	0.3672	ambiguous	0.354	ambiguous	-0.653	Destabilizing	0.996	D	0.652	neutral	None	None	None	None	N
S/Y	0.1758	likely_benign	0.1645	benign	-0.335	Destabilizing	0.979	D	0.593	neutral	N	0.482182112	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.