TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7033	21322;21323;21324	chr2:178724278;178724277;178724276	chr2:179589005;179589004;179589003
N2AB	6716	20371;20372;20373	chr2:178724278;178724277;178724276	chr2:179589005;179589004;179589003
N2A	5789	17590;17591;17592	chr2:178724278;178724277;178724276	chr2:179589005;179589004;179589003
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: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-54
• Domain position: 86
• Structural Position: 172
• Q(SASA): 0.1797
• 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/D	rs1176798251	-1.778	0.999	D	0.791	0.598	0.811951969987	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	0	None	0	0	0
A/D	rs1176798251	-1.778	0.999	D	0.791	0.598	0.811951969987	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
A/D	rs1176798251	-1.778	0.999	D	0.791	0.598	0.811951969987	gnomAD-4.0.0	6.57117E-06	None	None	None	None	N	None	2.41266E-05	0	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
A/C	0.667	likely_pathogenic	0.6436	pathogenic	-1.173	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
A/D	0.8615	likely_pathogenic	0.8334	pathogenic	-1.415	Destabilizing	0.999	D	0.791	deleterious	D	0.543344273	None	None	N
A/E	0.7743	likely_pathogenic	0.7397	pathogenic	-1.365	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
A/F	0.6737	likely_pathogenic	0.6022	pathogenic	-0.967	Destabilizing	0.995	D	0.764	deleterious	None	None	None	None	N
A/G	0.3796	ambiguous	0.3421	ambiguous	-1.377	Destabilizing	0.989	D	0.583	neutral	D	0.534449198	None	None	N
A/H	0.8925	likely_pathogenic	0.8784	pathogenic	-1.637	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
A/I	0.3446	ambiguous	0.3227	benign	-0.165	Destabilizing	0.967	D	0.696	prob.neutral	None	None	None	None	N
A/K	0.9193	likely_pathogenic	0.9124	pathogenic	-1.205	Destabilizing	0.998	D	0.746	deleterious	None	None	None	None	N
A/L	0.3752	ambiguous	0.3418	ambiguous	-0.165	Destabilizing	0.923	D	0.625	neutral	None	None	None	None	N
A/M	0.3505	ambiguous	0.3234	benign	-0.244	Destabilizing	0.923	D	0.577	neutral	None	None	None	None	N
A/N	0.7584	likely_pathogenic	0.7422	pathogenic	-1.095	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
A/P	0.9648	likely_pathogenic	0.9421	pathogenic	-0.407	Destabilizing	0.999	D	0.77	deleterious	D	0.543344273	None	None	N
A/Q	0.8187	likely_pathogenic	0.8031	pathogenic	-1.129	Destabilizing	0.998	D	0.753	deleterious	None	None	None	None	N
A/R	0.8579	likely_pathogenic	0.8461	pathogenic	-1.051	Destabilizing	0.998	D	0.766	deleterious	None	None	None	None	N
A/S	0.1683	likely_benign	0.1639	benign	-1.551	Destabilizing	0.989	D	0.571	neutral	N	0.4934356	None	None	N
A/T	0.1112	likely_benign	0.1099	benign	-1.382	Destabilizing	0.978	D	0.603	neutral	D	0.532600971	None	None	N
A/V	0.1362	likely_benign	0.1233	benign	-0.407	Destabilizing	0.37	N	0.401	neutral	N	0.509529324	None	None	N
A/W	0.9527	likely_pathogenic	0.9354	pathogenic	-1.43	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
A/Y	0.8508	likely_pathogenic	0.8163	pathogenic	-0.963	Destabilizing	0.999	D	0.791	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.