TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19020	57283;57284;57285	chr2:178598559;178598558;178598557	chr2:179463286;179463285;179463284
N2AB	17379	52360;52361;52362	chr2:178598559;178598558;178598557	chr2:179463286;179463285;179463284
N2A	16452	49579;49580;49581	chr2:178598559;178598558;178598557	chr2:179463286;179463285;179463284
N2B	9955	30088;30089;30090	chr2:178598559;178598558;178598557	chr2:179463286;179463285;179463284
Novex-1	10080	30463;30464;30465	chr2:178598559;178598558;178598557	chr2:179463286;179463285;179463284
Novex-2	10147	30664;30665;30666	chr2:178598559;178598558;178598557	chr2:179463286;179463285;179463284
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-26
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.3113
• 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
V/I	None	None	None	N	0.218	0.158	0.220303561663	gnomAD-4.0.0	1.20034E-06	None	None	None	None	I	None	0	1.01626E-03	None	0	0	None	0	0	0	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	0.8955	likely_pathogenic	0.8916	pathogenic	-1.871	Destabilizing	0.104	N	0.638	neutral	N	0.473334249	None	None	I
V/C	0.9579	likely_pathogenic	0.9579	pathogenic	-1.301	Destabilizing	0.968	D	0.731	prob.delet.	None	None	None	None	I
V/D	0.9855	likely_pathogenic	0.9839	pathogenic	-1.973	Destabilizing	0.726	D	0.851	deleterious	None	None	None	None	I
V/E	0.9654	likely_pathogenic	0.9597	pathogenic	-1.921	Destabilizing	0.667	D	0.829	deleterious	N	0.508835197	None	None	I
V/F	0.8168	likely_pathogenic	0.7988	pathogenic	-1.423	Destabilizing	0.567	D	0.779	deleterious	None	None	None	None	I
V/G	0.9266	likely_pathogenic	0.9187	pathogenic	-2.256	Highly Destabilizing	0.667	D	0.843	deleterious	N	0.508581707	None	None	I
V/H	0.9909	likely_pathogenic	0.9906	pathogenic	-1.824	Destabilizing	0.968	D	0.827	deleterious	None	None	None	None	I
V/I	0.0568	likely_benign	0.0559	benign	-0.876	Destabilizing	None	N	0.218	neutral	N	0.370173931	None	None	I
V/K	0.9736	likely_pathogenic	0.9682	pathogenic	-1.555	Destabilizing	0.726	D	0.831	deleterious	None	None	None	None	I
V/L	0.4186	ambiguous	0.392	ambiguous	-0.876	Destabilizing	0.009	N	0.428	neutral	N	0.47236251	None	None	I
V/M	0.5632	ambiguous	0.5618	ambiguous	-0.624	Destabilizing	0.567	D	0.654	neutral	None	None	None	None	I
V/N	0.9428	likely_pathogenic	0.9408	pathogenic	-1.452	Destabilizing	0.89	D	0.85	deleterious	None	None	None	None	I
V/P	0.8491	likely_pathogenic	0.8587	pathogenic	-1.175	Destabilizing	0.89	D	0.825	deleterious	None	None	None	None	I
V/Q	0.9733	likely_pathogenic	0.9714	pathogenic	-1.573	Destabilizing	0.89	D	0.821	deleterious	None	None	None	None	I
V/R	0.9679	likely_pathogenic	0.9595	pathogenic	-1.04	Destabilizing	0.726	D	0.853	deleterious	None	None	None	None	I
V/S	0.9495	likely_pathogenic	0.9447	pathogenic	-2.016	Highly Destabilizing	0.726	D	0.811	deleterious	None	None	None	None	I
V/T	0.8833	likely_pathogenic	0.8826	pathogenic	-1.847	Destabilizing	0.272	N	0.714	prob.delet.	None	None	None	None	I
V/W	0.9923	likely_pathogenic	0.9921	pathogenic	-1.7	Destabilizing	0.968	D	0.793	deleterious	None	None	None	None	I
V/Y	0.9698	likely_pathogenic	0.9658	pathogenic	-1.405	Destabilizing	0.726	D	0.758	deleterious	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.