TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6460	19603;19604;19605	chr2:178728548;178728547;178728546	chr2:179593275;179593274;179593273
N2AB	6143	18652;18653;18654	chr2:178728548;178728547;178728546	chr2:179593275;179593274;179593273
N2A	5216	15871;15872;15873	chr2:178728548;178728547;178728546	chr2:179593275;179593274;179593273
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-48
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.1708
• 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/G	rs766551817	-1.543	0.165	N	0.574	0.185	0.353548585375	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
E/G	rs766551817	-1.543	0.165	N	0.574	0.185	0.353548585375	gnomAD-4.0.0	2.73873E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69962E-06	0	1.6581E-05
E/V	None	None	0.324	N	0.576	0.215	0.348764635752	gnomAD-4.0.0	6.84682E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99875E-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	0.2622	likely_benign	0.2674	benign	-0.715	Destabilizing	0.003	N	0.163	neutral	N	0.481900005	None	None	N
E/C	0.9268	likely_pathogenic	0.9365	pathogenic	-0.247	Destabilizing	0.981	D	0.59	neutral	None	None	None	None	N
E/D	0.2751	likely_benign	0.3238	benign	-1.024	Destabilizing	0.001	N	0.113	neutral	N	0.513839065	None	None	N
E/F	0.8881	likely_pathogenic	0.9031	pathogenic	-0.702	Destabilizing	0.932	D	0.626	neutral	None	None	None	None	N
E/G	0.3152	likely_benign	0.3134	benign	-1.016	Destabilizing	0.165	N	0.574	neutral	N	0.508971963	None	None	N
E/H	0.6742	likely_pathogenic	0.7004	pathogenic	-1.028	Destabilizing	0.818	D	0.52	neutral	None	None	None	None	N
E/I	0.609	likely_pathogenic	0.6205	pathogenic	0.083	Stabilizing	0.818	D	0.607	neutral	None	None	None	None	N
E/K	0.3075	likely_benign	0.2706	benign	-0.259	Destabilizing	0.09	N	0.375	neutral	N	0.443610976	None	None	N
E/L	0.6949	likely_pathogenic	0.7098	pathogenic	0.083	Stabilizing	0.388	N	0.617	neutral	None	None	None	None	N
E/M	0.6225	likely_pathogenic	0.6403	pathogenic	0.56	Stabilizing	0.932	D	0.567	neutral	None	None	None	None	N
E/N	0.4837	ambiguous	0.5468	ambiguous	-0.589	Destabilizing	0.241	N	0.385	neutral	None	None	None	None	N
E/P	0.9949	likely_pathogenic	0.9943	pathogenic	-0.161	Destabilizing	0.563	D	0.491	neutral	None	None	None	None	N
E/Q	0.1676	likely_benign	0.1711	benign	-0.526	Destabilizing	0.018	N	0.266	neutral	N	0.438437229	None	None	N
E/R	0.4663	ambiguous	0.4315	ambiguous	-0.235	Destabilizing	0.388	N	0.453	neutral	None	None	None	None	N
E/S	0.2577	likely_benign	0.2792	benign	-0.878	Destabilizing	0.01	N	0.1	neutral	None	None	None	None	N
E/T	0.2943	likely_benign	0.2949	benign	-0.622	Destabilizing	0.241	N	0.465	neutral	None	None	None	None	N
E/V	0.391	ambiguous	0.388	ambiguous	-0.161	Destabilizing	0.324	N	0.576	neutral	N	0.491308922	None	None	N
E/W	0.952	likely_pathogenic	0.9564	pathogenic	-0.6	Destabilizing	0.981	D	0.652	neutral	None	None	None	None	N
E/Y	0.8391	likely_pathogenic	0.8584	pathogenic	-0.458	Destabilizing	0.932	D	0.599	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.