TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29462	88609;88610;88611	chr2:178555075;178555074;178555073	chr2:179419802;179419801;179419800
N2AB	27821	83686;83687;83688	chr2:178555075;178555074;178555073	chr2:179419802;179419801;179419800
N2A	26894	80905;80906;80907	chr2:178555075;178555074;178555073	chr2:179419802;179419801;179419800
N2B	20397	61414;61415;61416	chr2:178555075;178555074;178555073	chr2:179419802;179419801;179419800
Novex-1	20522	61789;61790;61791	chr2:178555075;178555074;178555073	chr2:179419802;179419801;179419800
Novex-2	20589	61990;61991;61992	chr2:178555075;178555074;178555073	chr2:179419802;179419801;179419800
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-146
• Domain position: 19
• Structural Position: 33
• Q(SASA): 0.1206
• 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/G	None	None	0.784	N	0.603	0.206	0.158396225186	gnomAD-4.0.0	1.59121E-06	None	None	None	None	N	None	0	0	None	0	2.77593E-05	None	0	0	0	0	0
A/T	None	None	0.425	N	0.59	0.131	0.128392430309	gnomAD-4.0.0	1.5912E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43283E-05	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	0.5221	ambiguous	0.5748	pathogenic	-0.726	Destabilizing	0.981	D	0.671	neutral	None	None	None	None	N
A/D	0.9785	likely_pathogenic	0.9795	pathogenic	-0.091	Destabilizing	0.975	D	0.751	deleterious	N	0.46141656	None	None	N
A/E	0.9582	likely_pathogenic	0.9605	pathogenic	-0.075	Destabilizing	0.828	D	0.693	prob.neutral	None	None	None	None	N
A/F	0.6721	likely_pathogenic	0.6953	pathogenic	-0.533	Destabilizing	0.003	N	0.505	neutral	None	None	None	None	N
A/G	0.3232	likely_benign	0.3159	benign	-0.799	Destabilizing	0.784	D	0.603	neutral	N	0.451573445	None	None	N
A/H	0.9667	likely_pathogenic	0.9715	pathogenic	-0.634	Destabilizing	0.981	D	0.774	deleterious	None	None	None	None	N
A/I	0.3851	ambiguous	0.4233	ambiguous	0.058	Stabilizing	0.013	N	0.511	neutral	None	None	None	None	N
A/K	0.9792	likely_pathogenic	0.9819	pathogenic	-0.6	Destabilizing	0.828	D	0.692	prob.neutral	None	None	None	None	N
A/L	0.3042	likely_benign	0.3485	ambiguous	0.058	Stabilizing	0.003	N	0.475	neutral	None	None	None	None	N
A/M	0.445	ambiguous	0.477	ambiguous	-0.24	Destabilizing	0.893	D	0.742	deleterious	None	None	None	None	N
A/N	0.9454	likely_pathogenic	0.952	pathogenic	-0.509	Destabilizing	0.981	D	0.759	deleterious	None	None	None	None	N
A/P	0.9405	likely_pathogenic	0.9465	pathogenic	-0.097	Destabilizing	0.975	D	0.728	prob.delet.	N	0.46141656	None	None	N
A/Q	0.9412	likely_pathogenic	0.9481	pathogenic	-0.51	Destabilizing	0.981	D	0.741	deleterious	None	None	None	None	N
A/R	0.9556	likely_pathogenic	0.9628	pathogenic	-0.433	Destabilizing	0.944	D	0.733	prob.delet.	None	None	None	None	N
A/S	0.3521	ambiguous	0.3622	ambiguous	-0.981	Destabilizing	0.784	D	0.601	neutral	N	0.492073273	None	None	N
A/T	0.2554	likely_benign	0.2772	benign	-0.83	Destabilizing	0.425	N	0.59	neutral	N	0.485704662	None	None	N
A/V	0.1648	likely_benign	0.185	benign	-0.097	Destabilizing	0.001	N	0.289	neutral	N	0.430328594	None	None	N
A/W	0.9618	likely_pathogenic	0.9659	pathogenic	-0.844	Destabilizing	0.995	D	0.791	deleterious	None	None	None	None	N
A/Y	0.8946	likely_pathogenic	0.9043	pathogenic	-0.392	Destabilizing	0.543	D	0.711	prob.delet.	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.