TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20071	60436;60437;60438	chr2:178591608;178591607;178591606	chr2:179456335;179456334;179456333
N2AB	18430	55513;55514;55515	chr2:178591608;178591607;178591606	chr2:179456335;179456334;179456333
N2A	17503	52732;52733;52734	chr2:178591608;178591607;178591606	chr2:179456335;179456334;179456333
N2B	11006	33241;33242;33243	chr2:178591608;178591607;178591606	chr2:179456335;179456334;179456333
Novex-1	11131	33616;33617;33618	chr2:178591608;178591607;178591606	chr2:179456335;179456334;179456333
Novex-2	11198	33817;33818;33819	chr2:178591608;178591607;178591606	chr2:179456335;179456334;179456333
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-33
• Domain position: 95
• Structural Position: 132
• Q(SASA): 0.9937
• 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
E/A	rs773208927	0.065	0.997	N	0.765	0.409	0.412715890961	gnomAD-2.1.1	2.03E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.69136E-04	None	0	0	0
E/A	rs773208927	0.065	0.997	N	0.765	0.409	0.412715890961	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	4.14938E-04	0
E/A	rs773208927	0.065	0.997	N	0.765	0.409	0.412715890961	gnomAD-4.0.0	1.48989E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.6688E-04	0
E/G	None	None	0.999	D	0.644	0.403	0.477451190609	gnomAD-4.0.0	6.85515E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.17498E-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
E/A	0.5007	ambiguous	0.4075	ambiguous	-0.114	Destabilizing	0.997	D	0.765	deleterious	N	0.464828823	None	None	N
E/C	0.9825	likely_pathogenic	0.9812	pathogenic	-0.097	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
E/D	0.2661	likely_benign	0.2566	benign	-0.156	Destabilizing	0.997	D	0.622	neutral	N	0.410052976	None	None	N
E/F	0.9819	likely_pathogenic	0.9783	pathogenic	-0.108	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/G	0.405	ambiguous	0.3508	ambiguous	-0.263	Destabilizing	0.999	D	0.644	neutral	D	0.527744151	None	None	N
E/H	0.9133	likely_pathogenic	0.8949	pathogenic	0.327	Stabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
E/I	0.8832	likely_pathogenic	0.8509	pathogenic	0.229	Stabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
E/K	0.6023	likely_pathogenic	0.5495	ambiguous	0.372	Stabilizing	0.997	D	0.76	deleterious	N	0.496258486	None	None	N
E/L	0.8643	likely_pathogenic	0.8318	pathogenic	0.229	Stabilizing	0.999	D	0.736	deleterious	None	None	None	None	N
E/M	0.889	likely_pathogenic	0.8572	pathogenic	0.092	Stabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
E/N	0.6456	likely_pathogenic	0.5762	pathogenic	0.208	Stabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
E/P	0.7516	likely_pathogenic	0.7133	pathogenic	0.134	Stabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
E/Q	0.4086	ambiguous	0.3398	benign	0.222	Stabilizing	0.999	D	0.673	prob.neutral	N	0.504789934	None	None	N
E/R	0.783	likely_pathogenic	0.755	pathogenic	0.597	Stabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
E/S	0.5927	likely_pathogenic	0.5099	ambiguous	0.019	Stabilizing	0.998	D	0.774	deleterious	None	None	None	None	N
E/T	0.7172	likely_pathogenic	0.6477	pathogenic	0.14	Stabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
E/V	0.7083	likely_pathogenic	0.6483	pathogenic	0.134	Stabilizing	0.999	D	0.75	deleterious	N	0.497272444	None	None	N
E/W	0.991	likely_pathogenic	0.9911	pathogenic	-0.033	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
E/Y	0.9568	likely_pathogenic	0.9488	pathogenic	0.12	Stabilizing	1.0	D	0.799	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.