TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9351	28276;28277;28278	chr2:178711185;178711184;178711183	chr2:179575912;179575911;179575910
N2AB	9034	27325;27326;27327	chr2:178711185;178711184;178711183	chr2:179575912;179575911;179575910
N2A	8107	24544;24545;24546	chr2:178711185;178711184;178711183	chr2:179575912;179575911;179575910
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: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-79
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.3276
• 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
F/L	None	None	0.008	None	0.308	0.261	0.232513804876	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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
F/A	0.8683	likely_pathogenic	0.9124	pathogenic	-1.932	Destabilizing	0.775	D	0.688	prob.neutral	None	None	None	None	N
F/C	0.6467	likely_pathogenic	0.7411	pathogenic	-1.118	Destabilizing	0.995	D	0.745	deleterious	None	None	None	None	N
F/D	0.9367	likely_pathogenic	0.9611	pathogenic	-0.095	Destabilizing	0.961	D	0.758	deleterious	None	None	None	None	N
F/E	0.9566	likely_pathogenic	0.9751	pathogenic	-0.009	Destabilizing	0.961	D	0.758	deleterious	None	None	None	None	N
F/G	0.9385	likely_pathogenic	0.9662	pathogenic	-2.26	Highly Destabilizing	0.961	D	0.731	prob.delet.	None	None	None	None	N
F/H	0.725	likely_pathogenic	0.7899	pathogenic	-0.617	Destabilizing	0.923	D	0.687	prob.neutral	None	None	None	None	N
F/I	0.3684	ambiguous	0.4292	ambiguous	-0.965	Destabilizing	0.565	D	0.595	neutral	None	None	None	None	N
F/K	0.9415	likely_pathogenic	0.9629	pathogenic	-0.949	Destabilizing	0.923	D	0.754	deleterious	None	None	None	None	N
F/L	0.898	likely_pathogenic	0.9275	pathogenic	-0.965	Destabilizing	0.008	N	0.308	neutral	None	None	None	None	N
F/M	0.7238	likely_pathogenic	0.7761	pathogenic	-0.785	Destabilizing	0.923	D	0.641	neutral	None	None	None	None	N
F/N	0.8268	likely_pathogenic	0.8844	pathogenic	-0.963	Destabilizing	0.961	D	0.755	deleterious	None	None	None	None	N
F/P	0.9939	likely_pathogenic	0.9975	pathogenic	-1.278	Destabilizing	0.987	D	0.75	deleterious	None	None	None	None	N
F/Q	0.911	likely_pathogenic	0.9433	pathogenic	-0.982	Destabilizing	0.961	D	0.755	deleterious	None	None	None	None	N
F/R	0.8753	likely_pathogenic	0.9133	pathogenic	-0.406	Destabilizing	0.961	D	0.756	deleterious	None	None	None	None	N
F/S	0.6975	likely_pathogenic	0.7779	pathogenic	-1.859	Destabilizing	0.901	D	0.719	prob.delet.	None	None	None	None	N
F/T	0.7925	likely_pathogenic	0.8485	pathogenic	-1.675	Destabilizing	0.961	D	0.717	prob.delet.	None	None	None	None	N
F/V	0.3824	ambiguous	0.4308	ambiguous	-1.278	Destabilizing	0.565	D	0.638	neutral	None	None	None	None	N
F/W	0.6462	likely_pathogenic	0.7513	pathogenic	-0.22	Destabilizing	0.989	D	0.642	neutral	None	None	None	None	N
F/Y	0.1685	likely_benign	0.2132	benign	-0.405	Destabilizing	0.003	N	0.278	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.