TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30568	91927;91928;91929	chr2:178550136;178550135;178550134	chr2:179414863;179414862;179414861
N2AB	28927	87004;87005;87006	chr2:178550136;178550135;178550134	chr2:179414863;179414862;179414861
N2A	28000	84223;84224;84225	chr2:178550136;178550135;178550134	chr2:179414863;179414862;179414861
N2B	21503	64732;64733;64734	chr2:178550136;178550135;178550134	chr2:179414863;179414862;179414861
Novex-1	21628	65107;65108;65109	chr2:178550136;178550135;178550134	chr2:179414863;179414862;179414861
Novex-2	21695	65308;65309;65310	chr2:178550136;178550135;178550134	chr2:179414863;179414862;179414861
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-149
• Domain position: 37
• Structural Position: 59
• Q(SASA): 0.5233
• 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	rs567700310	0.432	0.958	N	0.375	0.261	0.319114376414	gnomAD-2.1.1	5.63E-05	None	None	None	None	N	None	0	2.31736E-04	None	0	0	None	1.30719E-04	None	0	1.78E-05	0
E/K	rs567700310	0.432	0.958	N	0.375	0.261	0.319114376414	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
E/K	rs567700310	0.432	0.958	N	0.375	0.261	0.319114376414	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
E/K	rs567700310	0.432	0.958	N	0.375	0.261	0.319114376414	gnomAD-4.0.0	2.16891E-05	None	None	None	None	N	None	0	1.16667E-04	None	0	0	None	0	0	2.03433E-05	4.39252E-05	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	0.1458	likely_benign	0.1679	benign	-0.105	Destabilizing	0.625	D	0.335	neutral	N	0.468373347	None	None	N
E/C	0.7415	likely_pathogenic	0.7658	pathogenic	-0.269	Destabilizing	0.998	D	0.514	neutral	None	None	None	None	N
E/D	0.0968	likely_benign	0.1058	benign	-0.326	Destabilizing	0.002	N	0.167	neutral	N	0.446075278	None	None	N
E/F	0.6611	likely_pathogenic	0.7154	pathogenic	-0.005	Destabilizing	0.974	D	0.481	neutral	None	None	None	None	N
E/G	0.1218	likely_benign	0.1396	benign	-0.267	Destabilizing	0.801	D	0.417	neutral	N	0.490866205	None	None	N
E/H	0.3715	ambiguous	0.4178	ambiguous	0.543	Stabilizing	0.991	D	0.341	neutral	None	None	None	None	N
E/I	0.295	likely_benign	0.3483	ambiguous	0.276	Stabilizing	0.728	D	0.453	neutral	None	None	None	None	N
E/K	0.1419	likely_benign	0.1637	benign	0.319	Stabilizing	0.958	D	0.375	neutral	N	0.470834863	None	None	N
E/L	0.3216	likely_benign	0.377	ambiguous	0.276	Stabilizing	0.728	D	0.447	neutral	None	None	None	None	N
E/M	0.3998	ambiguous	0.4586	ambiguous	0.024	Stabilizing	0.993	D	0.473	neutral	None	None	None	None	N
E/N	0.192	likely_benign	0.2245	benign	-0.001	Destabilizing	0.728	D	0.338	neutral	None	None	None	None	N
E/P	0.3313	likely_benign	0.3725	ambiguous	0.168	Stabilizing	0.974	D	0.358	neutral	None	None	None	None	N
E/Q	0.1196	likely_benign	0.1318	benign	0.033	Stabilizing	0.954	D	0.384	neutral	N	0.478512983	None	None	N
E/R	0.2328	likely_benign	0.2598	benign	0.638	Stabilizing	0.974	D	0.35	neutral	None	None	None	None	N
E/S	0.1541	likely_benign	0.1801	benign	-0.149	Destabilizing	0.842	D	0.332	neutral	None	None	None	None	N
E/T	0.1626	likely_benign	0.1932	benign	-0.012	Destabilizing	0.842	D	0.342	neutral	None	None	None	None	N
E/V	0.1872	likely_benign	0.2196	benign	0.168	Stabilizing	0.051	N	0.305	neutral	N	0.47541675	None	None	N
E/W	0.8276	likely_pathogenic	0.8578	pathogenic	0.092	Stabilizing	0.998	D	0.581	neutral	None	None	None	None	N
E/Y	0.544	ambiguous	0.5888	pathogenic	0.229	Stabilizing	0.991	D	0.475	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.