TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5818	17677;17678;17679	chr2:178731314;178731313;178731312	chr2:179596041;179596040;179596039
N2AB	5501	16726;16727;16728	chr2:178731314;178731313;178731312	chr2:179596041;179596040;179596039
N2A	4574	13945;13946;13947	chr2:178731314;178731313;178731312	chr2:179596041;179596040;179596039
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-41
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.2693
• 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/L	rs749007462	-0.423	0.669	N	0.461	0.288	0.478828542108	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.81E-05	None	0	0	0
S/L	rs749007462	-0.423	0.669	N	0.461	0.288	0.478828542108	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07641E-04	0
S/L	rs749007462	-0.423	0.669	N	0.461	0.288	0.478828542108	gnomAD-4.0.0	6.19769E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.09823E-04	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	0.0739	likely_benign	0.0741	benign	-0.762	Destabilizing	0.005	N	0.107	neutral	N	0.439743951	None	None	N
S/C	0.1366	likely_benign	0.1552	benign	-0.429	Destabilizing	0.998	D	0.411	neutral	None	None	None	None	N
S/D	0.44	ambiguous	0.3799	ambiguous	0.186	Stabilizing	0.842	D	0.369	neutral	None	None	None	None	N
S/E	0.4935	ambiguous	0.4282	ambiguous	0.122	Stabilizing	0.842	D	0.369	neutral	None	None	None	None	N
S/F	0.1534	likely_benign	0.144	benign	-1.219	Destabilizing	0.974	D	0.509	neutral	None	None	None	None	N
S/G	0.1449	likely_benign	0.1475	benign	-0.912	Destabilizing	0.525	D	0.375	neutral	None	None	None	None	N
S/H	0.2851	likely_benign	0.2497	benign	-1.426	Destabilizing	0.998	D	0.412	neutral	None	None	None	None	N
S/I	0.1353	likely_benign	0.1198	benign	-0.481	Destabilizing	0.949	D	0.456	neutral	None	None	None	None	N
S/K	0.5752	likely_pathogenic	0.5049	ambiguous	-0.494	Destabilizing	0.842	D	0.362	neutral	None	None	None	None	N
S/L	0.0773	likely_benign	0.0786	benign	-0.481	Destabilizing	0.669	D	0.461	neutral	N	0.42462257	None	None	N
S/M	0.1527	likely_benign	0.1534	benign	-0.06	Destabilizing	0.991	D	0.417	neutral	None	None	None	None	N
S/N	0.1412	likely_benign	0.1273	benign	-0.245	Destabilizing	0.842	D	0.402	neutral	None	None	None	None	N
S/P	0.799	likely_pathogenic	0.8168	pathogenic	-0.546	Destabilizing	0.966	D	0.375	neutral	D	0.524266703	None	None	N
S/Q	0.4424	ambiguous	0.3981	ambiguous	-0.54	Destabilizing	0.974	D	0.403	neutral	None	None	None	None	N
S/R	0.4772	ambiguous	0.4068	ambiguous	-0.331	Destabilizing	0.949	D	0.385	neutral	None	None	None	None	N
S/T	0.0591	likely_benign	0.0576	benign	-0.424	Destabilizing	0.007	N	0.104	neutral	N	0.37819406	None	None	N
S/V	0.1356	likely_benign	0.1258	benign	-0.546	Destabilizing	0.728	D	0.461	neutral	None	None	None	None	N
S/W	0.2852	likely_benign	0.2635	benign	-1.113	Destabilizing	0.998	D	0.587	neutral	None	None	None	None	N
S/Y	0.1466	likely_benign	0.1359	benign	-0.872	Destabilizing	0.991	D	0.505	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.