TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16628	50107;50108;50109	chr2:178612839;178612838;178612837	chr2:179477566;179477565;179477564
N2AB	14987	45184;45185;45186	chr2:178612839;178612838;178612837	chr2:179477566;179477565;179477564
N2A	14060	42403;42404;42405	chr2:178612839;178612838;178612837	chr2:179477566;179477565;179477564
N2B	7563	22912;22913;22914	chr2:178612839;178612838;178612837	chr2:179477566;179477565;179477564
Novex-1	7688	23287;23288;23289	chr2:178612839;178612838;178612837	chr2:179477566;179477565;179477564
Novex-2	7755	23488;23489;23490	chr2:178612839;178612838;178612837	chr2:179477566;179477565;179477564
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-8
• Domain position: 78
• Structural Position: 111
• Q(SASA): 0.16
• 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
V/A	rs764958038	-2.227	0.998	N	0.435	0.432	0.613699239204	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
V/M	None	None	0.999	D	0.679	0.361	0.589963725375	gnomAD-4.0.0	1.36943E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.7997E-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
V/A	0.3807	ambiguous	0.4542	ambiguous	-1.908	Destabilizing	0.998	D	0.435	neutral	N	0.487762269	None	None	N
V/C	0.7811	likely_pathogenic	0.7849	pathogenic	-1.883	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
V/D	0.8155	likely_pathogenic	0.9055	pathogenic	-2.46	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
V/E	0.5478	ambiguous	0.6445	pathogenic	-2.377	Highly Destabilizing	1.0	D	0.775	deleterious	N	0.494986477	None	None	N
V/F	0.199	likely_benign	0.2564	benign	-1.378	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
V/G	0.4884	ambiguous	0.6211	pathogenic	-2.289	Highly Destabilizing	1.0	D	0.787	deleterious	D	0.65470174	None	None	N
V/H	0.7413	likely_pathogenic	0.7982	pathogenic	-1.723	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
V/I	0.0765	likely_benign	0.0706	benign	-0.907	Destabilizing	0.985	D	0.443	neutral	None	None	None	None	N
V/K	0.4721	ambiguous	0.5653	pathogenic	-1.514	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
V/L	0.2674	likely_benign	0.2801	benign	-0.907	Destabilizing	0.434	N	0.315	neutral	D	0.540432886	None	None	N
V/M	0.1907	likely_benign	0.1979	benign	-1.05	Destabilizing	0.999	D	0.679	prob.neutral	D	0.591555834	None	None	N
V/N	0.6153	likely_pathogenic	0.7117	pathogenic	-1.616	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
V/P	0.9884	likely_pathogenic	0.9936	pathogenic	-1.211	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
V/Q	0.4759	ambiguous	0.5245	ambiguous	-1.732	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
V/R	0.4214	ambiguous	0.5234	ambiguous	-1.082	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
V/S	0.4522	ambiguous	0.5479	ambiguous	-2.188	Highly Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
V/T	0.3379	likely_benign	0.3815	ambiguous	-1.988	Destabilizing	0.998	D	0.473	neutral	None	None	None	None	N
V/W	0.8697	likely_pathogenic	0.9074	pathogenic	-1.632	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
V/Y	0.6587	likely_pathogenic	0.7334	pathogenic	-1.321	Destabilizing	1.0	D	0.792	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.