TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24457	73594;73595;73596	chr2:178572763;178572762;178572761	chr2:179437490;179437489;179437488
N2AB	22816	68671;68672;68673	chr2:178572763;178572762;178572761	chr2:179437490;179437489;179437488
N2A	21889	65890;65891;65892	chr2:178572763;178572762;178572761	chr2:179437490;179437489;179437488
N2B	15392	46399;46400;46401	chr2:178572763;178572762;178572761	chr2:179437490;179437489;179437488
Novex-1	15517	46774;46775;46776	chr2:178572763;178572762;178572761	chr2:179437490;179437489;179437488
Novex-2	15584	46975;46976;46977	chr2:178572763;178572762;178572761	chr2:179437490;179437489;179437488
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-132
• Domain position: 27
• Structural Position: 43
• Q(SASA): 0.391
• 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
A/E	None	None	0.018	N	0.331	0.239	0.322510055762	gnomAD-4.0.0	1.59188E-06	None	None	None	None	I	None	0	0	None	0	2.77624E-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
A/C	0.4551	ambiguous	0.4615	ambiguous	-0.744	Destabilizing	0.989	D	0.491	neutral	None	None	None	None	I
A/D	0.2522	likely_benign	0.254	benign	-0.721	Destabilizing	0.858	D	0.571	neutral	None	None	None	None	I
A/E	0.2137	likely_benign	0.2193	benign	-0.879	Destabilizing	0.018	N	0.331	neutral	N	0.434047343	None	None	I
A/F	0.3106	likely_benign	0.3095	benign	-1.117	Destabilizing	0.923	D	0.645	neutral	None	None	None	None	I
A/G	0.2023	likely_benign	0.2136	benign	-0.587	Destabilizing	0.722	D	0.455	neutral	D	0.53469434	None	None	I
A/H	0.4612	ambiguous	0.4735	ambiguous	-0.683	Destabilizing	0.989	D	0.651	neutral	None	None	None	None	I
A/I	0.1417	likely_benign	0.1474	benign	-0.527	Destabilizing	0.372	N	0.481	neutral	None	None	None	None	I
A/K	0.4413	ambiguous	0.4645	ambiguous	-0.827	Destabilizing	0.633	D	0.45	neutral	None	None	None	None	I
A/L	0.1253	likely_benign	0.1262	benign	-0.527	Destabilizing	0.633	D	0.489	neutral	None	None	None	None	I
A/M	0.1566	likely_benign	0.1629	benign	-0.411	Destabilizing	0.979	D	0.508	neutral	None	None	None	None	I
A/N	0.2165	likely_benign	0.2253	benign	-0.417	Destabilizing	0.923	D	0.621	neutral	None	None	None	None	I
A/P	0.1145	likely_benign	0.116	benign	-0.489	Destabilizing	0.949	D	0.485	neutral	N	0.472509731	None	None	I
A/Q	0.2865	likely_benign	0.3	benign	-0.745	Destabilizing	0.858	D	0.481	neutral	None	None	None	None	I
A/R	0.454	ambiguous	0.4705	ambiguous	-0.327	Destabilizing	0.923	D	0.48	neutral	None	None	None	None	I
A/S	0.0906	likely_benign	0.0919	benign	-0.608	Destabilizing	0.565	D	0.511	neutral	N	0.504024716	None	None	I
A/T	0.072	likely_benign	0.0721	benign	-0.695	Destabilizing	0.018	N	0.277	neutral	N	0.403399149	None	None	I
A/V	0.0833	likely_benign	0.0844	benign	-0.489	Destabilizing	0.008	N	0.279	neutral	N	0.496733385	None	None	I
A/W	0.7548	likely_pathogenic	0.7588	pathogenic	-1.24	Destabilizing	0.996	D	0.703	prob.neutral	None	None	None	None	I
A/Y	0.456	ambiguous	0.4685	ambiguous	-0.911	Destabilizing	0.961	D	0.645	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.