TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15383	46372;46373;46374	chr2:178620374;178620373;178620372	chr2:179485101;179485100;179485099
N2AB	13742	41449;41450;41451	chr2:178620374;178620373;178620372	chr2:179485101;179485100;179485099
N2A	12815	38668;38669;38670	chr2:178620374;178620373;178620372	chr2:179485101;179485100;179485099
N2B	6318	19177;19178;19179	chr2:178620374;178620373;178620372	chr2:179485101;179485100;179485099
Novex-1	6443	19552;19553;19554	chr2:178620374;178620373;178620372	chr2:179485101;179485100;179485099
Novex-2	6510	19753;19754;19755	chr2:178620374;178620373;178620372	chr2:179485101;179485100;179485099
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-105
• Domain position: 82
• Structural Position: 173
• Q(SASA): 0.5276
• 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	rs773073914	None	0.865	N	0.524	0.186	None	gnomAD-4.0.0	6.854E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.0052E-07	0	0
E/Q	rs773073914	-0.909	0.284	N	0.235	0.128	0.159798565429	gnomAD-2.1.1	1.08E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.58E-05	1.41563E-04
E/Q	rs773073914	-0.909	0.284	N	0.235	0.128	0.159798565429	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	6.57E-05	0	0	0	None	0	0	4.42E-05	0	0
E/Q	rs773073914	-0.909	0.284	N	0.235	0.128	0.159798565429	gnomAD-4.0.0	3.35225E-05	None	None	None	None	N	None	0	1.67398E-05	None	0	0	None	0	0	4.24311E-05	0	4.81217E-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	0.4564	ambiguous	0.4415	ambiguous	-0.863	Destabilizing	0.865	D	0.65	neutral	N	0.486170681	None	None	N
E/C	0.952	likely_pathogenic	0.9573	pathogenic	-0.408	Destabilizing	0.999	D	0.758	deleterious	None	None	None	None	N
E/D	0.3398	likely_benign	0.3853	ambiguous	-1.042	Destabilizing	0.928	D	0.474	neutral	N	0.437284274	None	None	N
E/F	0.924	likely_pathogenic	0.9303	pathogenic	-0.27	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
E/G	0.4765	ambiguous	0.4821	ambiguous	-1.232	Destabilizing	0.978	D	0.739	prob.delet.	D	0.531210132	None	None	N
E/H	0.69	likely_pathogenic	0.677	pathogenic	-0.504	Destabilizing	0.996	D	0.699	prob.neutral	None	None	None	None	N
E/I	0.7733	likely_pathogenic	0.7908	pathogenic	0.144	Stabilizing	0.992	D	0.773	deleterious	None	None	None	None	N
E/K	0.3041	likely_benign	0.2424	benign	-0.425	Destabilizing	0.865	D	0.524	neutral	N	0.448488372	None	None	N
E/L	0.7959	likely_pathogenic	0.7914	pathogenic	0.144	Stabilizing	0.983	D	0.775	deleterious	None	None	None	None	N
E/M	0.7956	likely_pathogenic	0.8116	pathogenic	0.573	Stabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
E/N	0.4837	ambiguous	0.5123	ambiguous	-0.97	Destabilizing	0.983	D	0.706	prob.neutral	None	None	None	None	N
E/P	0.9626	likely_pathogenic	0.955	pathogenic	-0.17	Destabilizing	0.992	D	0.801	deleterious	None	None	None	None	N
E/Q	0.2458	likely_benign	0.232	benign	-0.834	Destabilizing	0.284	N	0.235	neutral	N	0.450883314	None	None	N
E/R	0.4483	ambiguous	0.3741	ambiguous	-0.162	Destabilizing	0.968	D	0.711	prob.delet.	None	None	None	None	N
E/S	0.3996	ambiguous	0.4175	ambiguous	-1.276	Destabilizing	0.895	D	0.606	neutral	None	None	None	None	N
E/T	0.4918	ambiguous	0.5102	ambiguous	-0.961	Destabilizing	0.983	D	0.784	deleterious	None	None	None	None	N
E/V	0.5807	likely_pathogenic	0.6011	pathogenic	-0.17	Destabilizing	0.978	D	0.777	deleterious	N	0.483091997	None	None	N
E/W	0.9738	likely_pathogenic	0.9761	pathogenic	0.021	Stabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
E/Y	0.8674	likely_pathogenic	0.8615	pathogenic	0.009	Stabilizing	0.992	D	0.776	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.