TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5424	16495;16496;16497	chr2:178732906;178732905;178732904	chr2:179597633;179597632;179597631
N2AB	5107	15544;15545;15546	chr2:178732906;178732905;178732904	chr2:179597633;179597632;179597631
N2A	4180	12763;12764;12765	chr2:178732906;178732905;178732904	chr2:179597633;179597632;179597631
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-37
• Domain position: 68
• Structural Position: 151
• Q(SASA): 0.2224
• 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
A/S	None	None	0.014	N	0.148	0.114	0.16115917748	gnomAD-4.0.0	3.18415E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86599E-05	0
A/V	rs1466084495	-0.412	0.565	D	0.452	0.318	None	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
A/V	rs1466084495	-0.412	0.565	D	0.452	0.318	None	gnomAD-4.0.0	1.59207E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85894E-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
A/C	0.5085	ambiguous	0.5331	ambiguous	-0.873	Destabilizing	0.996	D	0.447	neutral	None	None	None	None	N
A/D	0.3583	ambiguous	0.4612	ambiguous	-0.686	Destabilizing	0.923	D	0.623	neutral	None	None	None	None	N
A/E	0.2488	likely_benign	0.3257	benign	-0.755	Destabilizing	0.722	D	0.533	neutral	N	0.472720374	None	None	N
A/F	0.3733	ambiguous	0.4108	ambiguous	-1.013	Destabilizing	0.923	D	0.693	prob.neutral	None	None	None	None	N
A/G	0.1388	likely_benign	0.1506	benign	-0.963	Destabilizing	0.565	D	0.452	neutral	N	0.502429993	None	None	N
A/H	0.4896	ambiguous	0.5664	pathogenic	-1.058	Destabilizing	0.989	D	0.679	prob.neutral	None	None	None	None	N
A/I	0.2597	likely_benign	0.2768	benign	-0.359	Destabilizing	0.024	N	0.306	neutral	None	None	None	None	N
A/K	0.3579	ambiguous	0.4503	ambiguous	-0.997	Destabilizing	0.633	D	0.529	neutral	None	None	None	None	N
A/L	0.2348	likely_benign	0.2625	benign	-0.359	Destabilizing	0.415	N	0.531	neutral	None	None	None	None	N
A/M	0.2271	likely_benign	0.2463	benign	-0.318	Destabilizing	0.923	D	0.591	neutral	None	None	None	None	N
A/N	0.3012	likely_benign	0.3638	ambiguous	-0.693	Destabilizing	0.858	D	0.625	neutral	None	None	None	None	N
A/P	0.6746	likely_pathogenic	0.7089	pathogenic	-0.45	Destabilizing	0.949	D	0.59	neutral	N	0.487595795	None	None	N
A/Q	0.3184	likely_benign	0.3767	ambiguous	-0.876	Destabilizing	0.923	D	0.596	neutral	None	None	None	None	N
A/R	0.2817	likely_benign	0.3457	ambiguous	-0.628	Destabilizing	0.923	D	0.588	neutral	None	None	None	None	N
A/S	0.0938	likely_benign	0.0995	benign	-1.056	Destabilizing	0.014	N	0.148	neutral	N	0.408612968	None	None	N
A/T	0.0893	likely_benign	0.091	benign	-1.024	Destabilizing	0.565	D	0.445	neutral	N	0.500928483	None	None	N
A/V	0.1354	likely_benign	0.1422	benign	-0.45	Destabilizing	0.565	D	0.452	neutral	D	0.522727907	None	None	N
A/W	0.7668	likely_pathogenic	0.8091	pathogenic	-1.274	Destabilizing	0.996	D	0.739	prob.delet.	None	None	None	None	N
A/Y	0.5092	ambiguous	0.5798	pathogenic	-0.881	Destabilizing	0.987	D	0.699	prob.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.