TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6514	19765;19766;19767	chr2:178728284;178728283;178728282	chr2:179593011;179593010;179593009
N2AB	6197	18814;18815;18816	chr2:178728284;178728283;178728282	chr2:179593011;179593010;179593009
N2A	5270	16033;16034;16035	chr2:178728284;178728283;178728282	chr2:179593011;179593010;179593009
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: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Ig-49
• Domain position: 34
• Structural Position: 48
• Q(SASA): 0.1177
• 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
W/C	None	None	0.056	D	0.76	0.889	0.887458683018	gnomAD-4.0.0	4.79107E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.2976E-06	0	0
W/L	rs760007747	-1.991	0.805	D	0.802	0.781	None	gnomAD-2.1.1	2.51E-05	None	None	None	None	N	None	4.14E-05	0	None	0	0	None	0	None	0	4.71E-05	0
W/L	rs760007747	-1.991	0.805	D	0.802	0.781	None	gnomAD-3.1.2	5.26E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	8.82E-05	0	0
W/L	rs760007747	-1.991	0.805	D	0.802	0.781	None	gnomAD-4.0.0	5.20729E-05	None	None	None	None	N	None	2.67144E-05	0	None	0	0	None	0	0	6.69755E-05	0	4.80615E-05

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
W/A	0.984	likely_pathogenic	0.9879	pathogenic	-3.05	Highly Destabilizing	0.845	D	0.824	deleterious	None	None	None	None	N
W/C	0.9908	likely_pathogenic	0.9935	pathogenic	-1.54	Destabilizing	0.056	N	0.76	deleterious	D	0.700511641	None	None	N
W/D	0.9988	likely_pathogenic	0.9987	pathogenic	-3.547	Highly Destabilizing	0.996	D	0.857	deleterious	None	None	None	None	N
W/E	0.9986	likely_pathogenic	0.9987	pathogenic	-3.431	Highly Destabilizing	0.996	D	0.861	deleterious	None	None	None	None	N
W/F	0.571	likely_pathogenic	0.5936	pathogenic	-1.927	Destabilizing	0.987	D	0.781	deleterious	None	None	None	None	N
W/G	0.9515	likely_pathogenic	0.9615	pathogenic	-3.282	Highly Destabilizing	0.983	D	0.813	deleterious	D	0.716329197	None	None	N
W/H	0.9942	likely_pathogenic	0.9948	pathogenic	-2.357	Highly Destabilizing	0.999	D	0.824	deleterious	None	None	None	None	N
W/I	0.9169	likely_pathogenic	0.9312	pathogenic	-2.151	Highly Destabilizing	0.975	D	0.861	deleterious	None	None	None	None	N
W/K	0.9992	likely_pathogenic	0.9993	pathogenic	-2.448	Highly Destabilizing	0.987	D	0.858	deleterious	None	None	None	None	N
W/L	0.8411	likely_pathogenic	0.8717	pathogenic	-2.151	Highly Destabilizing	0.805	D	0.802	deleterious	D	0.716329198	None	None	N
W/M	0.9707	likely_pathogenic	0.9768	pathogenic	-1.556	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
W/N	0.9976	likely_pathogenic	0.9979	pathogenic	-3.179	Highly Destabilizing	0.996	D	0.871	deleterious	None	None	None	None	N
W/P	0.9976	likely_pathogenic	0.9979	pathogenic	-2.481	Highly Destabilizing	0.996	D	0.869	deleterious	None	None	None	None	N
W/Q	0.9989	likely_pathogenic	0.9992	pathogenic	-3.008	Highly Destabilizing	0.996	D	0.858	deleterious	None	None	None	None	N
W/R	0.9983	likely_pathogenic	0.9985	pathogenic	-2.247	Highly Destabilizing	0.994	D	0.868	deleterious	D	0.716531002	None	None	N
W/S	0.9853	likely_pathogenic	0.9884	pathogenic	-3.268	Highly Destabilizing	0.967	D	0.849	deleterious	D	0.716531002	None	None	N
W/T	0.9874	likely_pathogenic	0.9901	pathogenic	-3.077	Highly Destabilizing	0.975	D	0.807	deleterious	None	None	None	None	N
W/V	0.9263	likely_pathogenic	0.944	pathogenic	-2.481	Highly Destabilizing	0.95	D	0.843	deleterious	None	None	None	None	N
W/Y	0.8535	likely_pathogenic	0.8625	pathogenic	-1.78	Destabilizing	0.996	D	0.787	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.