TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5580	16963;16964;16965	chr2:178732231;178732230;178732229	chr2:179596958;179596957;179596956
N2AB	5263	16012;16013;16014	chr2:178732231;178732230;178732229	chr2:179596958;179596957;179596956
N2A	4336	13231;13232;13233	chr2:178732231;178732230;178732229	chr2:179596958;179596957;179596956
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-39
• Domain position: 38
• Structural Position: 51
• Q(SASA): 0.4825
• 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
N/D	rs376598696	None	0.02	N	0.235	0.087	None	gnomAD-2.1.1	2.14E-05	None	None	None	None	N	None	2.48036E-04	0	None	0	0	None	0	None	0	0	0
N/D	rs376598696	None	0.02	N	0.235	0.087	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
N/D	rs376598696	None	0.02	N	0.235	0.087	None	gnomAD-4.0.0	8.96753E-06	None	None	None	None	N	None	1.18399E-04	0	None	0	0	None	0	0	0	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
N/A	0.1894	likely_benign	0.2079	benign	-0.612	Destabilizing	0.953	D	0.533	neutral	None	None	None	None	N
N/C	0.2772	likely_benign	0.3276	benign	0.304	Stabilizing	0.999	D	0.669	neutral	None	None	None	None	N
N/D	0.0945	likely_benign	0.1021	benign	0.026	Stabilizing	0.02	N	0.235	neutral	N	0.455341682	None	None	N
N/E	0.2889	likely_benign	0.3048	benign	0.023	Stabilizing	0.91	D	0.432	neutral	None	None	None	None	N
N/F	0.4975	ambiguous	0.5497	ambiguous	-0.785	Destabilizing	0.999	D	0.678	prob.neutral	None	None	None	None	N
N/G	0.1546	likely_benign	0.1626	benign	-0.841	Destabilizing	0.953	D	0.419	neutral	None	None	None	None	N
N/H	0.0961	likely_benign	0.1049	benign	-0.83	Destabilizing	0.997	D	0.518	neutral	N	0.51791228	None	None	N
N/I	0.3622	ambiguous	0.4144	ambiguous	-0.081	Destabilizing	0.991	D	0.707	prob.neutral	N	0.511671309	None	None	N
N/K	0.1886	likely_benign	0.198	benign	-0.084	Destabilizing	0.939	D	0.449	neutral	N	0.477144639	None	None	N
N/L	0.2733	likely_benign	0.3012	benign	-0.081	Destabilizing	0.993	D	0.695	prob.neutral	None	None	None	None	N
N/M	0.3549	ambiguous	0.3886	ambiguous	0.378	Stabilizing	0.999	D	0.613	neutral	None	None	None	None	N
N/P	0.7888	likely_pathogenic	0.8241	pathogenic	-0.231	Destabilizing	0.993	D	0.621	neutral	None	None	None	None	N
N/Q	0.2318	likely_benign	0.2498	benign	-0.515	Destabilizing	0.993	D	0.505	neutral	None	None	None	None	N
N/R	0.2029	likely_benign	0.2169	benign	-0.063	Destabilizing	0.993	D	0.51	neutral	None	None	None	None	N
N/S	0.0772	likely_benign	0.0817	benign	-0.36	Destabilizing	0.939	D	0.431	neutral	N	0.475916872	None	None	N
N/T	0.1974	likely_benign	0.2207	benign	-0.201	Destabilizing	0.969	D	0.445	neutral	N	0.51116433	None	None	N
N/V	0.3327	likely_benign	0.3793	ambiguous	-0.231	Destabilizing	0.993	D	0.699	prob.neutral	None	None	None	None	N
N/W	0.6659	likely_pathogenic	0.7088	pathogenic	-0.673	Destabilizing	0.999	D	0.662	neutral	None	None	None	None	N
N/Y	0.1651	likely_benign	0.1839	benign	-0.461	Destabilizing	0.997	D	0.615	neutral	N	0.503277518	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.