TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5825	17698;17699;17700	chr2:178731192;178731191;178731190	chr2:179595919;179595918;179595917
N2AB	5508	16747;16748;16749	chr2:178731192;178731191;178731190	chr2:179595919;179595918;179595917
N2A	4581	13966;13967;13968	chr2:178731192;178731191;178731190	chr2:179595919;179595918;179595917
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: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-42
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.1247
• 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/V	rs778914141	-1.331	0.4	N	0.281	0.217	0.516938183928	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	0	8.71E-05	None	0	0	None	0	None	0	8.88E-06	1.66168E-04
I/V	rs778914141	-1.331	0.4	N	0.281	0.217	0.516938183928	gnomAD-4.0.0	1.11509E-05	None	None	None	None	N	None	0	1.14453E-04	None	0	0	None	0	0	5.72361E-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	0.8901	likely_pathogenic	0.8966	pathogenic	-2.203	Highly Destabilizing	0.985	D	0.749	deleterious	None	None	None	None	N
I/C	0.9574	likely_pathogenic	0.958	pathogenic	-1.972	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
I/D	0.9949	likely_pathogenic	0.9953	pathogenic	-2.04	Highly Destabilizing	0.999	D	0.893	deleterious	None	None	None	None	N
I/E	0.9872	likely_pathogenic	0.9893	pathogenic	-1.925	Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
I/F	0.5365	ambiguous	0.5155	ambiguous	-1.533	Destabilizing	0.265	N	0.466	neutral	N	0.507715595	None	None	N
I/G	0.9879	likely_pathogenic	0.9884	pathogenic	-2.627	Highly Destabilizing	0.999	D	0.874	deleterious	None	None	None	None	N
I/H	0.983	likely_pathogenic	0.9842	pathogenic	-1.896	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
I/K	0.9577	likely_pathogenic	0.9649	pathogenic	-1.492	Destabilizing	0.999	D	0.889	deleterious	None	None	None	None	N
I/L	0.3739	ambiguous	0.3701	ambiguous	-1.038	Destabilizing	0.817	D	0.556	neutral	N	0.506220256	None	None	N
I/M	0.304	likely_benign	0.3109	benign	-1.183	Destabilizing	0.997	D	0.725	prob.delet.	D	0.526859406	None	None	N
I/N	0.938	likely_pathogenic	0.9438	pathogenic	-1.595	Destabilizing	0.999	D	0.888	deleterious	D	0.528126854	None	None	N
I/P	0.9706	likely_pathogenic	0.9747	pathogenic	-1.401	Destabilizing	0.999	D	0.89	deleterious	None	None	None	None	N
I/Q	0.9743	likely_pathogenic	0.9764	pathogenic	-1.659	Destabilizing	0.999	D	0.905	deleterious	None	None	None	None	N
I/R	0.9399	likely_pathogenic	0.9491	pathogenic	-1.08	Destabilizing	0.999	D	0.89	deleterious	None	None	None	None	N
I/S	0.94	likely_pathogenic	0.9451	pathogenic	-2.336	Highly Destabilizing	0.997	D	0.85	deleterious	D	0.527873364	None	None	N
I/T	0.9119	likely_pathogenic	0.9223	pathogenic	-2.087	Highly Destabilizing	0.98	D	0.823	deleterious	D	0.527619875	None	None	N
I/V	0.0948	likely_benign	0.0953	benign	-1.401	Destabilizing	0.4	N	0.281	neutral	N	0.489330542	None	None	N
I/W	0.9811	likely_pathogenic	0.9782	pathogenic	-1.681	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
I/Y	0.9341	likely_pathogenic	0.9333	pathogenic	-1.407	Destabilizing	0.991	D	0.809	deleterious	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.