TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14387	43384;43385;43386	chr2:178632972;178632971;178632970	chr2:179497699;179497698;179497697
N2AB	12746	38461;38462;38463	chr2:178632972;178632971;178632970	chr2:179497699;179497698;179497697
N2A	11819	35680;35681;35682	chr2:178632972;178632971;178632970	chr2:179497699;179497698;179497697
N2B	5322	16189;16190;16191	chr2:178632972;178632971;178632970	chr2:179497699;179497698;179497697
Novex-1	5447	16564;16565;16566	chr2:178632972;178632971;178632970	chr2:179497699;179497698;179497697
Novex-2	5514	16765;16766;16767	chr2:178632972;178632971;178632970	chr2:179497699;179497698;179497697
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-94
• Domain position: 69
• Structural Position: 153
• Q(SASA): 0.2753
• 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	0.104	N	0.609	0.163	0.183819452728	gnomAD-4.0.0	1.59251E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86079E-06	0	0
E/Q	None	None	0.007	N	0.267	0.064	0.139678290688	gnomAD-4.0.0	6.84439E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99717E-07	0	0
E/V	rs749959242	0.009	0.449	N	0.665	0.239	0.30921473904	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
E/V	rs749959242	0.009	0.449	N	0.665	0.239	0.30921473904	gnomAD-4.0.0	4.77754E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.58236E-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	0.233	likely_benign	0.2343	benign	-0.611	Destabilizing	0.104	N	0.609	neutral	N	0.435532453	None	None	N
E/C	0.9399	likely_pathogenic	0.9464	pathogenic	-0.024	Destabilizing	0.962	D	0.649	prob.neutral	None	None	None	None	N
E/D	0.2292	likely_benign	0.225	benign	-0.825	Destabilizing	0.189	N	0.496	neutral	N	0.495490775	None	None	N
E/F	0.8818	likely_pathogenic	0.8811	pathogenic	-0.739	Destabilizing	0.962	D	0.697	prob.delet.	None	None	None	None	N
E/G	0.3817	ambiguous	0.4104	ambiguous	-0.862	Destabilizing	0.449	N	0.638	neutral	N	0.440025561	None	None	N
E/H	0.7106	likely_pathogenic	0.7034	pathogenic	-0.97	Destabilizing	0.892	D	0.623	neutral	None	None	None	None	N
E/I	0.4438	ambiguous	0.4223	ambiguous	0.035	Stabilizing	0.687	D	0.758	deleterious	None	None	None	None	N
E/K	0.1733	likely_benign	0.1678	benign	0.02	Stabilizing	0.001	N	0.281	neutral	N	0.463380104	None	None	N
E/L	0.568	likely_pathogenic	0.5446	ambiguous	0.035	Stabilizing	0.519	D	0.648	neutral	None	None	None	None	N
E/M	0.5349	ambiguous	0.5178	ambiguous	0.483	Stabilizing	0.892	D	0.717	prob.delet.	None	None	None	None	N
E/N	0.4092	ambiguous	0.3982	ambiguous	-0.25	Destabilizing	0.519	D	0.603	neutral	None	None	None	None	N
E/P	0.6858	likely_pathogenic	0.6786	pathogenic	-0.16	Destabilizing	0.687	D	0.719	prob.delet.	None	None	None	None	N
E/Q	0.2303	likely_benign	0.2217	benign	-0.233	Destabilizing	0.007	N	0.267	neutral	N	0.447370046	None	None	N
E/R	0.3616	ambiguous	0.3583	ambiguous	0.019	Stabilizing	0.134	N	0.59	neutral	None	None	None	None	N
E/S	0.3569	ambiguous	0.36	ambiguous	-0.474	Destabilizing	0.134	N	0.493	neutral	None	None	None	None	N
E/T	0.3002	likely_benign	0.2828	benign	-0.268	Destabilizing	0.519	D	0.696	prob.delet.	None	None	None	None	N
E/V	0.2873	likely_benign	0.2765	benign	-0.16	Destabilizing	0.449	N	0.665	prob.neutral	N	0.410979012	None	None	N
E/W	0.9608	likely_pathogenic	0.9612	pathogenic	-0.656	Destabilizing	0.962	D	0.641	neutral	None	None	None	None	N
E/Y	0.8212	likely_pathogenic	0.8237	pathogenic	-0.498	Destabilizing	0.687	D	0.757	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.