TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7682	23269;23270;23271	chr2:178720975;178720974;178720973	chr2:179585702;179585701;179585700
N2AB	7365	22318;22319;22320	chr2:178720975;178720974;178720973	chr2:179585702;179585701;179585700
N2A	6438	19537;19538;19539	chr2:178720975;178720974;178720973	chr2:179585702;179585701;179585700
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: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-61
• Domain position: 75
• Structural Position: 157
• Q(SASA): 0.3001
• 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/K	rs761584703	-0.891	0.999	N	0.669	0.367	None	gnomAD-2.1.1	2.02E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	4.46E-05	0
E/K	rs761584703	-0.891	0.999	N	0.669	0.367	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
E/K	rs761584703	-0.891	0.999	N	0.669	0.367	None	gnomAD-4.0.0	3.1094E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.56421E-05	1.64962E-04	3.99964E-05	0	1.60689E-05

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	0.2759	likely_benign	0.4269	ambiguous	-1.01	Destabilizing	0.997	D	0.734	prob.delet.	N	0.492872033	None	None	N
E/C	0.9391	likely_pathogenic	0.9681	pathogenic	-0.62	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
E/D	0.4829	ambiguous	0.6632	pathogenic	-1.395	Destabilizing	0.981	D	0.589	neutral	N	0.513382598	None	None	N
E/F	0.8463	likely_pathogenic	0.9343	pathogenic	-0.655	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
E/G	0.473	ambiguous	0.6798	pathogenic	-1.408	Destabilizing	1.0	D	0.82	deleterious	D	0.531993832	None	None	N
E/H	0.5576	ambiguous	0.777	pathogenic	-1.054	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
E/I	0.3854	ambiguous	0.5512	ambiguous	0.091	Stabilizing	0.999	D	0.899	deleterious	None	None	None	None	N
E/K	0.125	likely_benign	0.2827	benign	-0.959	Destabilizing	0.999	D	0.669	neutral	N	0.457116204	None	None	N
E/L	0.5099	ambiguous	0.6925	pathogenic	0.091	Stabilizing	0.999	D	0.869	deleterious	None	None	None	None	N
E/M	0.5044	ambiguous	0.6712	pathogenic	0.715	Stabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
E/N	0.5503	ambiguous	0.7787	pathogenic	-1.371	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
E/P	0.9952	likely_pathogenic	0.9979	pathogenic	-0.256	Destabilizing	0.996	D	0.866	deleterious	None	None	None	None	N
E/Q	0.1392	likely_benign	0.2338	benign	-1.184	Destabilizing	0.999	D	0.711	prob.delet.	N	0.502715207	None	None	N
E/R	0.2475	likely_benign	0.4838	ambiguous	-0.828	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
E/S	0.3918	ambiguous	0.5969	pathogenic	-1.811	Destabilizing	0.998	D	0.729	prob.delet.	None	None	None	None	N
E/T	0.3441	ambiguous	0.559	ambiguous	-1.462	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
E/V	0.2245	likely_benign	0.3229	benign	-0.256	Destabilizing	0.999	D	0.866	deleterious	N	0.445592488	None	None	N
E/W	0.9558	likely_pathogenic	0.9857	pathogenic	-0.535	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
E/Y	0.7802	likely_pathogenic	0.911	pathogenic	-0.427	Destabilizing	1.0	D	0.887	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.