TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29920	89983;89984;89985	chr2:178553142;178553141;178553140	chr2:179417869;179417868;179417867
N2AB	28279	85060;85061;85062	chr2:178553142;178553141;178553140	chr2:179417869;179417868;179417867
N2A	27352	82279;82280;82281	chr2:178553142;178553141;178553140	chr2:179417869;179417868;179417867
N2B	20855	62788;62789;62790	chr2:178553142;178553141;178553140	chr2:179417869;179417868;179417867
Novex-1	20980	63163;63164;63165	chr2:178553142;178553141;178553140	chr2:179417869;179417868;179417867
Novex-2	21047	63364;63365;63366	chr2:178553142;178553141;178553140	chr2:179417869;179417868;179417867
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-147
• Domain position: 79
• Structural Position: 165
• Q(SASA): 0.5236
• Predicted PPI site: I

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	rs747181293	-0.286	0.052	N	0.349	0.106	0.186928172975	gnomAD-2.1.1	8.06E-05	None	None	None	None	I	None	0	4.35111E-04	None	0	0	None	0	None	0	2.67E-05	3.33E-04
E/D	rs747181293	-0.286	0.052	N	0.349	0.106	0.186928172975	gnomAD-3.1.2	5.26E-05	None	None	None	None	I	None	0	6.54E-05	0	0	0	None	0	0	8.82E-05	0	4.77555E-04
E/D	rs747181293	-0.286	0.052	N	0.349	0.106	0.186928172975	gnomAD-4.0.0	4.09236E-05	None	None	None	None	I	None	0	3.6674E-04	None	0	0	None	0	0	3.30783E-05	0	8.01E-05
E/G	None	None	0.117	N	0.477	0.334	0.358340041657	gnomAD-4.0.0	1.59379E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43377E-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	0.1167	likely_benign	0.1301	benign	-0.038	Destabilizing	0.027	N	0.407	neutral	N	0.505643656	None	None	I
E/C	0.7801	likely_pathogenic	0.785	pathogenic	-0.253	Destabilizing	0.935	D	0.527	neutral	None	None	None	None	I
E/D	0.1279	likely_benign	0.1221	benign	-0.324	Destabilizing	0.052	N	0.349	neutral	N	0.513975138	None	None	I
E/F	0.6298	likely_pathogenic	0.6419	pathogenic	-0.095	Destabilizing	0.791	D	0.487	neutral	None	None	None	None	I
E/G	0.1404	likely_benign	0.1518	benign	-0.144	Destabilizing	0.117	N	0.477	neutral	N	0.489775069	None	None	I
E/H	0.3299	likely_benign	0.3602	ambiguous	0.547	Stabilizing	0.38	N	0.403	neutral	None	None	None	None	I
E/I	0.2327	likely_benign	0.2352	benign	0.18	Stabilizing	0.555	D	0.491	neutral	None	None	None	None	I
E/K	0.0925	likely_benign	0.105	benign	0.346	Stabilizing	None	N	0.247	neutral	N	0.49434644	None	None	I
E/L	0.2384	likely_benign	0.2547	benign	0.18	Stabilizing	0.149	N	0.515	neutral	None	None	None	None	I
E/M	0.3195	likely_benign	0.3223	benign	-0.067	Destabilizing	0.824	D	0.481	neutral	None	None	None	None	I
E/N	0.1889	likely_benign	0.2009	benign	0.143	Stabilizing	0.149	N	0.398	neutral	None	None	None	None	I
E/P	0.2299	likely_benign	0.2714	benign	0.125	Stabilizing	0.001	N	0.305	neutral	None	None	None	None	I
E/Q	0.0844	likely_benign	0.0957	benign	0.143	Stabilizing	None	N	0.22	neutral	N	0.486191104	None	None	I
E/R	0.1868	likely_benign	0.2089	benign	0.595	Stabilizing	0.081	N	0.357	neutral	None	None	None	None	I
E/S	0.1491	likely_benign	0.1587	benign	-0.009	Destabilizing	0.081	N	0.34	neutral	None	None	None	None	I
E/T	0.1549	likely_benign	0.1628	benign	0.085	Stabilizing	0.149	N	0.453	neutral	None	None	None	None	I
E/V	0.1576	likely_benign	0.1573	benign	0.125	Stabilizing	0.117	N	0.481	neutral	N	0.503720859	None	None	I
E/W	0.8452	likely_pathogenic	0.8598	pathogenic	-0.053	Destabilizing	0.935	D	0.559	neutral	None	None	None	None	I
E/Y	0.5164	ambiguous	0.5225	ambiguous	0.127	Stabilizing	0.555	D	0.484	neutral	None	None	None	None	I

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.