TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10107	30544;30545;30546	chr2:178702568;178702567;178702566	chr2:179567295;179567294;179567293
N2AB	9790	29593;29594;29595	chr2:178702568;178702567;178702566	chr2:179567295;179567294;179567293
N2A	8863	26812;26813;26814	chr2:178702568;178702567;178702566	chr2:179567295;179567294;179567293
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-86
• Domain position: 30
• Structural Position: 45
• Q(SASA): 0.6934
• 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
I/T	None	None	0.801	None	0.572	0.259	0.683524595578	gnomAD-4.0.0	1.59085E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85745E-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
I/A	0.8228	likely_pathogenic	0.7722	pathogenic	-0.788	Destabilizing	0.525	D	0.506	neutral	None	None	None	None	N
I/C	0.9822	likely_pathogenic	0.9749	pathogenic	-0.544	Destabilizing	0.998	D	0.525	neutral	None	None	None	None	N
I/D	0.971	likely_pathogenic	0.9701	pathogenic	-0.412	Destabilizing	0.016	N	0.35	neutral	None	None	None	None	N
I/E	0.9107	likely_pathogenic	0.8972	pathogenic	-0.493	Destabilizing	0.728	D	0.586	neutral	None	None	None	None	N
I/F	0.6787	likely_pathogenic	0.6164	pathogenic	-0.715	Destabilizing	0.934	D	0.553	neutral	None	None	None	None	N
I/G	0.9829	likely_pathogenic	0.979	pathogenic	-0.979	Destabilizing	0.915	D	0.599	neutral	None	None	None	None	N
I/H	0.9499	likely_pathogenic	0.935	pathogenic	-0.23	Destabilizing	0.998	D	0.575	neutral	None	None	None	None	N
I/K	0.8653	likely_pathogenic	0.8381	pathogenic	-0.481	Destabilizing	0.974	D	0.604	neutral	None	None	None	None	N
I/L	0.4205	ambiguous	0.3769	ambiguous	-0.394	Destabilizing	0.267	N	0.297	neutral	None	None	None	None	N
I/M	0.3526	ambiguous	0.3233	benign	-0.411	Destabilizing	0.966	D	0.547	neutral	None	None	None	None	N
I/N	0.8589	likely_pathogenic	0.8562	pathogenic	-0.227	Destabilizing	0.934	D	0.602	neutral	None	None	None	None	N
I/P	0.9835	likely_pathogenic	0.989	pathogenic	-0.492	Destabilizing	0.991	D	0.617	neutral	None	None	None	None	N
I/Q	0.9102	likely_pathogenic	0.888	pathogenic	-0.464	Destabilizing	0.974	D	0.611	neutral	None	None	None	None	N
I/R	0.8295	likely_pathogenic	0.7851	pathogenic	0.114	Stabilizing	0.974	D	0.613	neutral	None	None	None	None	N
I/S	0.8466	likely_pathogenic	0.8241	pathogenic	-0.669	Destabilizing	0.801	D	0.587	neutral	None	None	None	None	N
I/T	0.6183	likely_pathogenic	0.5314	ambiguous	-0.643	Destabilizing	0.801	D	0.572	neutral	None	None	None	None	N
I/V	0.1593	likely_benign	0.1035	benign	-0.492	Destabilizing	0.005	N	0.16	neutral	None	None	None	None	N
I/W	0.9752	likely_pathogenic	0.9767	pathogenic	-0.736	Destabilizing	0.998	D	0.64	neutral	None	None	None	None	N
I/Y	0.932	likely_pathogenic	0.9285	pathogenic	-0.498	Destabilizing	0.974	D	0.581	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.