TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7838	23737;23738;23739	chr2:178720130;178720129;178720128	chr2:179584857;179584856;179584855
N2AB	7521	22786;22787;22788	chr2:178720130;178720129;178720128	chr2:179584857;179584856;179584855
N2A	6594	20005;20006;20007	chr2:178720130;178720129;178720128	chr2:179584857;179584856;179584855
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-63
• Domain position: 44
• Structural Position: 70
• Q(SASA): 0.3473
• 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	None	N	0.153	0.117	0.159798565429	gnomAD-4.0.0	1.59141E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85871E-06	0	0
E/K	rs891050085	0.11	0.38	N	0.323	0.368	0.348764635752	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
E/K	rs891050085	0.11	0.38	N	0.323	0.368	0.348764635752	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	4.79386E-04
E/K	rs891050085	0.11	0.38	N	0.323	0.368	0.348764635752	gnomAD-4.0.0	3.84346E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78677E-06	0	2.84495E-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	0.2989	likely_benign	0.242	benign	-0.315	Destabilizing	0.248	N	0.332	neutral	N	0.507393095	None	None	N
E/C	0.9748	likely_pathogenic	0.9653	pathogenic	-0.095	Destabilizing	0.973	D	0.453	neutral	None	None	None	None	N
E/D	0.2523	likely_benign	0.2354	benign	-0.357	Destabilizing	None	N	0.153	neutral	N	0.51724473	None	None	N
E/F	0.9478	likely_pathogenic	0.9293	pathogenic	-0.104	Destabilizing	0.852	D	0.418	neutral	None	None	None	None	N
E/G	0.3156	likely_benign	0.2647	benign	-0.507	Destabilizing	0.524	D	0.357	neutral	N	0.498458348	None	None	N
E/H	0.8478	likely_pathogenic	0.8097	pathogenic	0.253	Stabilizing	0.926	D	0.323	neutral	None	None	None	None	N
E/I	0.7725	likely_pathogenic	0.7046	pathogenic	0.154	Stabilizing	0.012	N	0.329	neutral	None	None	None	None	N
E/K	0.4398	ambiguous	0.3792	ambiguous	0.488	Stabilizing	0.38	N	0.323	neutral	N	0.504748544	None	None	N
E/L	0.7758	likely_pathogenic	0.7071	pathogenic	0.154	Stabilizing	0.16	N	0.372	neutral	None	None	None	None	N
E/M	0.8151	likely_pathogenic	0.759	pathogenic	0.138	Stabilizing	0.646	D	0.4	neutral	None	None	None	None	N
E/N	0.5634	ambiguous	0.4985	ambiguous	-0.026	Destabilizing	0.081	N	0.31	neutral	None	None	None	None	N
E/P	0.5594	ambiguous	0.4911	ambiguous	0.017	Stabilizing	0.287	N	0.353	neutral	None	None	None	None	N
E/Q	0.3231	likely_benign	0.2774	benign	0.038	Stabilizing	0.47	N	0.361	neutral	N	0.494379744	None	None	N
E/R	0.6474	likely_pathogenic	0.5868	pathogenic	0.706	Stabilizing	0.852	D	0.327	neutral	None	None	None	None	N
E/S	0.4624	ambiguous	0.3977	ambiguous	-0.121	Destabilizing	0.305	N	0.293	neutral	None	None	None	None	N
E/T	0.5695	likely_pathogenic	0.4955	ambiguous	0.051	Stabilizing	0.377	N	0.36	neutral	None	None	None	None	N
E/V	0.5353	ambiguous	0.4644	ambiguous	0.017	Stabilizing	0.092	N	0.365	neutral	N	0.49705277	None	None	N
E/W	0.9809	likely_pathogenic	0.9743	pathogenic	0.072	Stabilizing	0.994	D	0.536	neutral	None	None	None	None	N
E/Y	0.9	likely_pathogenic	0.8657	pathogenic	0.152	Stabilizing	0.979	D	0.405	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.