TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19113	57562;57563;57564	chr2:178597745;178597744;178597743	chr2:179462472;179462471;179462470
N2AB	17472	52639;52640;52641	chr2:178597745;178597744;178597743	chr2:179462472;179462471;179462470
N2A	16545	49858;49859;49860	chr2:178597745;178597744;178597743	chr2:179462472;179462471;179462470
N2B	10048	30367;30368;30369	chr2:178597745;178597744;178597743	chr2:179462472;179462471;179462470
Novex-1	10173	30742;30743;30744	chr2:178597745;178597744;178597743	chr2:179462472;179462471;179462470
Novex-2	10240	30943;30944;30945	chr2:178597745;178597744;178597743	chr2:179462472;179462471;179462470
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-117
• Domain position: 19
• Structural Position: 31
• Q(SASA): 0.2831
• 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
I/T	None	None	0.997	N	0.591	0.401	0.817057561884	gnomAD-4.0.0	1.59239E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02627E-05
I/V	rs2052104416	None	0.798	N	0.4	0.143	0.59589940523	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.07125E-04	0
I/V	rs2052104416	None	0.798	N	0.4	0.143	0.59589940523	gnomAD-4.0.0	2.56395E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.68053E-05	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	0.7606	likely_pathogenic	0.8323	pathogenic	-1.724	Destabilizing	0.992	D	0.438	neutral	None	None	None	None	I
I/C	0.9377	likely_pathogenic	0.9517	pathogenic	-1.01	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	I
I/D	0.982	likely_pathogenic	0.9886	pathogenic	-0.61	Destabilizing	0.999	D	0.766	deleterious	None	None	None	None	I
I/E	0.968	likely_pathogenic	0.9737	pathogenic	-0.539	Destabilizing	0.999	D	0.75	deleterious	None	None	None	None	I
I/F	0.468	ambiguous	0.5903	pathogenic	-1.057	Destabilizing	0.994	D	0.587	neutral	N	0.455097406	None	None	I
I/G	0.9558	likely_pathogenic	0.9708	pathogenic	-2.113	Highly Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	I
I/H	0.9125	likely_pathogenic	0.9386	pathogenic	-1.27	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	I
I/K	0.9073	likely_pathogenic	0.9325	pathogenic	-0.913	Destabilizing	0.999	D	0.734	prob.delet.	None	None	None	None	I
I/L	0.1638	likely_benign	0.1913	benign	-0.701	Destabilizing	0.054	N	0.243	neutral	N	0.443533618	None	None	I
I/M	0.1965	likely_benign	0.258	benign	-0.603	Destabilizing	0.994	D	0.595	neutral	N	0.478704984	None	None	I
I/N	0.8161	likely_pathogenic	0.8747	pathogenic	-0.798	Destabilizing	0.999	D	0.769	deleterious	N	0.426619938	None	None	I
I/P	0.9059	likely_pathogenic	0.9634	pathogenic	-1.012	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	I
I/Q	0.9062	likely_pathogenic	0.9232	pathogenic	-0.864	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	I
I/R	0.8546	likely_pathogenic	0.8956	pathogenic	-0.498	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	I
I/S	0.7962	likely_pathogenic	0.8552	pathogenic	-1.591	Destabilizing	0.999	D	0.645	neutral	N	0.451035593	None	None	I
I/T	0.5654	likely_pathogenic	0.6783	pathogenic	-1.388	Destabilizing	0.997	D	0.591	neutral	N	0.42896681	None	None	I
I/V	0.1842	likely_benign	0.2291	benign	-1.012	Destabilizing	0.798	D	0.4	neutral	N	0.448728794	None	None	I
I/W	0.9391	likely_pathogenic	0.9597	pathogenic	-1.142	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
I/Y	0.868	likely_pathogenic	0.9096	pathogenic	-0.891	Destabilizing	0.999	D	0.677	prob.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.