TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5489	16690;16691;16692	chr2:178732596;178732595;178732594	chr2:179597323;179597322;179597321
N2AB	5172	15739;15740;15741	chr2:178732596;178732595;178732594	chr2:179597323;179597322;179597321
N2A	4245	12958;12959;12960	chr2:178732596;178732595;178732594	chr2:179597323;179597322;179597321
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-38
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.6112
• 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/D	None	None	0.977	D	0.475	0.269	0.267755039894	gnomAD-4.0.0	6.84254E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99496E-07	0	0
E/K	rs1171851091	0.46	0.117	N	0.334	0.232	0.357929162469	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	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	0.2321	likely_benign	0.2837	benign	-0.546	Destabilizing	0.977	D	0.589	neutral	D	0.533790263	None	None	N
E/C	0.9391	likely_pathogenic	0.9567	pathogenic	-0.428	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
E/D	0.3515	ambiguous	0.4424	ambiguous	-0.684	Destabilizing	0.977	D	0.475	neutral	D	0.528883088	None	None	N
E/F	0.8944	likely_pathogenic	0.941	pathogenic	0.196	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
E/G	0.4448	ambiguous	0.5678	pathogenic	-0.878	Destabilizing	0.993	D	0.594	neutral	N	0.49335624	None	None	N
E/H	0.7732	likely_pathogenic	0.8493	pathogenic	0.318	Stabilizing	1.0	D	0.663	neutral	None	None	None	None	N
E/I	0.4745	ambiguous	0.5824	pathogenic	0.349	Stabilizing	0.998	D	0.725	prob.delet.	None	None	None	None	N
E/K	0.3366	likely_benign	0.4574	ambiguous	-0.144	Destabilizing	0.117	N	0.334	neutral	N	0.483971263	None	None	N
E/L	0.4712	ambiguous	0.5712	pathogenic	0.349	Stabilizing	0.995	D	0.7	prob.neutral	None	None	None	None	N
E/M	0.5468	ambiguous	0.6357	pathogenic	0.42	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
E/N	0.565	likely_pathogenic	0.6803	pathogenic	-0.816	Destabilizing	0.995	D	0.646	neutral	None	None	None	None	N
E/P	0.4644	ambiguous	0.5074	ambiguous	0.072	Stabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	N
E/Q	0.2428	likely_benign	0.291	benign	-0.673	Destabilizing	0.977	D	0.571	neutral	N	0.492315829	None	None	N
E/R	0.5372	ambiguous	0.6502	pathogenic	0.281	Stabilizing	0.99	D	0.629	neutral	None	None	None	None	N
E/S	0.4798	ambiguous	0.5982	pathogenic	-1.037	Destabilizing	0.983	D	0.596	neutral	None	None	None	None	N
E/T	0.4734	ambiguous	0.5854	pathogenic	-0.75	Destabilizing	0.995	D	0.651	neutral	None	None	None	None	N
E/V	0.2752	likely_benign	0.3523	ambiguous	0.072	Stabilizing	0.997	D	0.689	prob.neutral	D	0.529096519	None	None	N
E/W	0.9704	likely_pathogenic	0.9831	pathogenic	0.499	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
E/Y	0.8245	likely_pathogenic	0.8935	pathogenic	0.474	Stabilizing	0.999	D	0.695	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.