TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17423	52492;52493;52494	chr2:178608744;178608743;178608742	chr2:179473471;179473470;179473469
N2AB	15782	47569;47570;47571	chr2:178608744;178608743;178608742	chr2:179473471;179473470;179473469
N2A	14855	44788;44789;44790	chr2:178608744;178608743;178608742	chr2:179473471;179473470;179473469
N2B	8358	25297;25298;25299	chr2:178608744;178608743;178608742	chr2:179473471;179473470;179473469
Novex-1	8483	25672;25673;25674	chr2:178608744;178608743;178608742	chr2:179473471;179473470;179473469
Novex-2	8550	25873;25874;25875	chr2:178608744;178608743;178608742	chr2:179473471;179473470;179473469
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: Fn3-14
• Domain position: 55
• Structural Position: 70
• Q(SASA): 0.7163
• Predicted PPI site: I

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	None	None	0.317	D	0.343	0.203	0.262175524916	gnomAD-4.0.0	1.59378E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86207E-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	0.0955	likely_benign	0.0777	benign	-0.475	Destabilizing	None	N	0.13	neutral	N	0.480787205	None	None	I
S/C	0.2658	likely_benign	0.2272	benign	-0.244	Destabilizing	0.824	D	0.327	neutral	None	None	None	None	I
S/D	0.6952	likely_pathogenic	0.7147	pathogenic	-0.283	Destabilizing	0.149	N	0.372	neutral	None	None	None	None	I
S/E	0.7593	likely_pathogenic	0.7662	pathogenic	-0.381	Destabilizing	0.149	N	0.377	neutral	None	None	None	None	I
S/F	0.6841	likely_pathogenic	0.6166	pathogenic	-1.126	Destabilizing	0.38	N	0.408	neutral	None	None	None	None	I
S/G	0.1307	likely_benign	0.1185	benign	-0.573	Destabilizing	0.081	N	0.376	neutral	None	None	None	None	I
S/H	0.6665	likely_pathogenic	0.665	pathogenic	-1.17	Destabilizing	0.935	D	0.333	neutral	None	None	None	None	I
S/I	0.6599	likely_pathogenic	0.5864	pathogenic	-0.339	Destabilizing	0.081	N	0.415	neutral	None	None	None	None	I
S/K	0.8802	likely_pathogenic	0.8905	pathogenic	-0.485	Destabilizing	0.149	N	0.376	neutral	None	None	None	None	I
S/L	0.3097	likely_benign	0.2597	benign	-0.339	Destabilizing	None	N	0.257	neutral	N	0.480137288	None	None	I
S/M	0.4399	ambiguous	0.3787	ambiguous	0.167	Stabilizing	0.38	N	0.328	neutral	None	None	None	None	I
S/N	0.2984	likely_benign	0.2974	benign	-0.242	Destabilizing	0.262	N	0.442	neutral	None	None	None	None	I
S/P	0.5367	ambiguous	0.5213	ambiguous	-0.357	Destabilizing	0.317	N	0.343	neutral	D	0.524348768	None	None	I
S/Q	0.6867	likely_pathogenic	0.6823	pathogenic	-0.608	Destabilizing	0.555	D	0.335	neutral	None	None	None	None	I
S/R	0.868	likely_pathogenic	0.8797	pathogenic	-0.218	Destabilizing	0.38	N	0.343	neutral	None	None	None	None	I
S/T	0.1314	likely_benign	0.1173	benign	-0.335	Destabilizing	0.002	N	0.229	neutral	N	0.460374648	None	None	I
S/V	0.5027	ambiguous	0.4176	ambiguous	-0.357	Destabilizing	0.081	N	0.411	neutral	None	None	None	None	I
S/W	0.7842	likely_pathogenic	0.7616	pathogenic	-1.094	Destabilizing	0.935	D	0.533	neutral	None	None	None	None	I
S/Y	0.5756	likely_pathogenic	0.5397	ambiguous	-0.819	Destabilizing	0.555	D	0.401	neutral	None	None	None	None	I

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.