TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5862	17809;17810;17811	chr2:178731081;178731080;178731079	chr2:179595808;179595807;179595806
N2AB	5545	16858;16859;16860	chr2:178731081;178731080;178731079	chr2:179595808;179595807;179595806
N2A	4618	14077;14078;14079	chr2:178731081;178731080;178731079	chr2:179595808;179595807;179595806
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-42
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.4421
• 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	rs756303980	0.271	0.999	D	0.646	0.439	0.541105671861	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
E/K	rs756303980	0.271	0.999	D	0.646	0.439	0.541105671861	gnomAD-4.0.0	2.05274E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69854E-06	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	0.1294	likely_benign	0.1434	benign	-0.595	Destabilizing	0.999	D	0.669	neutral	D	0.525440138	None	None	N
E/C	0.8161	likely_pathogenic	0.8737	pathogenic	-0.366	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
E/D	0.3018	likely_benign	0.352	ambiguous	-0.673	Destabilizing	0.999	D	0.495	neutral	D	0.524573347	None	None	N
E/F	0.7558	likely_pathogenic	0.8242	pathogenic	0.052	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
E/G	0.2281	likely_benign	0.2824	benign	-0.91	Destabilizing	1.0	D	0.674	neutral	N	0.512448	None	None	N
E/H	0.5459	ambiguous	0.6555	pathogenic	0.181	Stabilizing	1.0	D	0.659	neutral	None	None	None	None	N
E/I	0.2678	likely_benign	0.3054	benign	0.247	Stabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
E/K	0.1496	likely_benign	0.2065	benign	-0.049	Destabilizing	0.999	D	0.646	neutral	D	0.530056524	None	None	N
E/L	0.2968	likely_benign	0.3436	ambiguous	0.247	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/M	0.3534	ambiguous	0.3968	ambiguous	0.355	Stabilizing	1.0	D	0.659	neutral	None	None	None	None	N
E/N	0.3938	ambiguous	0.4644	ambiguous	-0.689	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
E/P	0.2674	likely_benign	0.2873	benign	-0.013	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
E/Q	0.1285	likely_benign	0.1495	benign	-0.562	Destabilizing	1.0	D	0.614	neutral	D	0.52526678	None	None	N
E/R	0.2762	likely_benign	0.3724	ambiguous	0.341	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
E/S	0.2888	likely_benign	0.3397	benign	-0.89	Destabilizing	0.999	D	0.655	neutral	None	None	None	None	N
E/T	0.2648	likely_benign	0.3142	benign	-0.619	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
E/V	0.1595	likely_benign	0.1772	benign	-0.013	Destabilizing	1.0	D	0.726	prob.delet.	D	0.531790108	None	None	N
E/W	0.9244	likely_pathogenic	0.9521	pathogenic	0.359	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
E/Y	0.66	likely_pathogenic	0.7571	pathogenic	0.335	Stabilizing	1.0	D	0.687	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.