TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31989	96190;96191;96192	chr2:178544264;178544263;178544262	chr2:179408991;179408990;179408989
N2AB	30348	91267;91268;91269	chr2:178544264;178544263;178544262	chr2:179408991;179408990;179408989
N2A	29421	88486;88487;88488	chr2:178544264;178544263;178544262	chr2:179408991;179408990;179408989
N2B	22924	68995;68996;68997	chr2:178544264;178544263;178544262	chr2:179408991;179408990;179408989
Novex-1	23049	69370;69371;69372	chr2:178544264;178544263;178544262	chr2:179408991;179408990;179408989
Novex-2	23116	69571;69572;69573	chr2:178544264;178544263;178544262	chr2:179408991;179408990;179408989
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-121
• Domain position: 81
• Structural Position: 112
• Q(SASA): 0.1012
• 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
N/K	rs775762346	None	1.0	N	0.738	0.475	0.0551355673512	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/K	rs775762346	None	1.0	N	0.738	0.475	0.0551355673512	gnomAD-4.0.0	3.09866E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.23822E-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
N/A	0.9692	likely_pathogenic	0.9633	pathogenic	-0.695	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
N/C	0.8773	likely_pathogenic	0.8539	pathogenic	-0.55	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
N/D	0.9403	likely_pathogenic	0.9347	pathogenic	-2.17	Highly Destabilizing	0.999	D	0.593	neutral	D	0.526498606	None	None	I
N/E	0.996	likely_pathogenic	0.9951	pathogenic	-2.012	Highly Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	I
N/F	0.9977	likely_pathogenic	0.9969	pathogenic	-0.58	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	I
N/G	0.9217	likely_pathogenic	0.911	pathogenic	-1.009	Destabilizing	0.999	D	0.551	neutral	None	None	None	None	I
N/H	0.9097	likely_pathogenic	0.9034	pathogenic	-0.72	Destabilizing	1.0	D	0.769	deleterious	D	0.539033453	None	None	I
N/I	0.9812	likely_pathogenic	0.976	pathogenic	0.106	Stabilizing	1.0	D	0.792	deleterious	D	0.539540432	None	None	I
N/K	0.9963	likely_pathogenic	0.9957	pathogenic	-0.264	Destabilizing	1.0	D	0.738	prob.delet.	N	0.52016873	None	None	I
N/L	0.9517	likely_pathogenic	0.9377	pathogenic	0.106	Stabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
N/M	0.9797	likely_pathogenic	0.9747	pathogenic	0.327	Stabilizing	1.0	D	0.808	deleterious	None	None	None	None	I
N/P	0.9923	likely_pathogenic	0.9906	pathogenic	-0.133	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
N/Q	0.9938	likely_pathogenic	0.993	pathogenic	-1.171	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
N/R	0.9939	likely_pathogenic	0.9925	pathogenic	-0.22	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
N/S	0.4296	ambiguous	0.4163	ambiguous	-1.066	Destabilizing	0.999	D	0.575	neutral	N	0.491376052	None	None	I
N/T	0.7672	likely_pathogenic	0.7704	pathogenic	-0.755	Destabilizing	0.999	D	0.699	prob.neutral	N	0.490447318	None	None	I
N/V	0.9745	likely_pathogenic	0.9686	pathogenic	-0.133	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
N/W	0.9992	likely_pathogenic	0.9989	pathogenic	-0.547	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	I
N/Y	0.9806	likely_pathogenic	0.9751	pathogenic	-0.134	Destabilizing	1.0	D	0.797	deleterious	D	0.539286943	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.