TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8608	26047;26048;26049	chr2:178715592;178715591;178715590	chr2:179580319;179580318;179580317
N2AB	8291	25096;25097;25098	chr2:178715592;178715591;178715590	chr2:179580319;179580318;179580317
N2A	7364	22315;22316;22317	chr2:178715592;178715591;178715590	chr2:179580319;179580318;179580317
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-71
• Domain position: 60
• Structural Position: 139
• Q(SASA): 0.2728
• 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	None	None	0.987	N	0.521	0.409	0.476051820916	gnomAD-4.0.0	6.84262E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99536E-07	0	0
E/G	None	None	0.998	D	0.615	0.508	0.582764979894	gnomAD-4.0.0	6.84262E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99536E-07	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
E/A	0.3068	likely_benign	0.3048	benign	-1.36	Destabilizing	0.987	D	0.521	neutral	N	0.487845604	None	None	N
E/C	0.9289	likely_pathogenic	0.9247	pathogenic	-1.017	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
E/D	0.3161	likely_benign	0.3229	benign	-1.772	Destabilizing	0.029	N	0.387	neutral	N	0.486479705	None	None	N
E/F	0.8313	likely_pathogenic	0.8346	pathogenic	-0.876	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
E/G	0.456	ambiguous	0.4695	ambiguous	-1.78	Destabilizing	0.998	D	0.615	neutral	D	0.528613244	None	None	N
E/H	0.553	ambiguous	0.5566	ambiguous	-1.172	Destabilizing	1.0	D	0.628	neutral	None	None	None	None	N
E/I	0.4332	ambiguous	0.4305	ambiguous	-0.164	Destabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	N
E/K	0.2825	likely_benign	0.2907	benign	-1.888	Destabilizing	0.986	D	0.504	neutral	N	0.494674514	None	None	N
E/L	0.5097	ambiguous	0.5004	ambiguous	-0.164	Destabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	N
E/M	0.5523	ambiguous	0.5484	ambiguous	0.557	Stabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
E/N	0.5131	ambiguous	0.5301	ambiguous	-2.148	Highly Destabilizing	0.993	D	0.6	neutral	None	None	None	None	N
E/P	0.9906	likely_pathogenic	0.9905	pathogenic	-0.545	Destabilizing	0.996	D	0.707	prob.neutral	None	None	None	None	N
E/Q	0.1538	likely_benign	0.1526	benign	-1.85	Destabilizing	0.9	D	0.35	neutral	N	0.468258704	None	None	N
E/R	0.3984	ambiguous	0.4166	ambiguous	-1.642	Destabilizing	0.998	D	0.593	neutral	None	None	None	None	N
E/S	0.3699	ambiguous	0.3738	ambiguous	-2.741	Highly Destabilizing	0.99	D	0.517	neutral	None	None	None	None	N
E/T	0.3272	likely_benign	0.3317	benign	-2.374	Highly Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
E/V	0.2518	likely_benign	0.2459	benign	-0.545	Destabilizing	0.997	D	0.692	prob.neutral	N	0.488671262	None	None	N
E/W	0.9251	likely_pathogenic	0.9261	pathogenic	-0.928	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
E/Y	0.7388	likely_pathogenic	0.7412	pathogenic	-0.753	Destabilizing	1.0	D	0.703	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.