TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5851	17776;17777;17778	chr2:178731114;178731113;178731112	chr2:179595841;179595840;179595839
N2AB	5534	16825;16826;16827	chr2:178731114;178731113;178731112	chr2:179595841;179595840;179595839
N2A	4607	14044;14045;14046	chr2:178731114;178731113;178731112	chr2:179595841;179595840;179595839
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-42
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.9007
• 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/G	rs547188027	0.064	0.117	N	0.462	0.248	0.384752662912	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
E/G	rs547188027	0.064	0.117	N	0.462	0.248	0.384752662912	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
E/G	rs547188027	0.064	0.117	N	0.462	0.248	0.384752662912	gnomAD-4.0.0	6.56832E-06	None	None	None	None	I	None	0	6.54622E-05	None	0	0	None	0	0	0	0	0
E/K	rs878877605	0.697	0.117	N	0.339	0.24	None	gnomAD-2.1.1	1.07E-05	None	None	None	None	I	None	1.23987E-04	0	None	0	0	None	0	None	0	0	0
E/K	rs878877605	0.697	0.117	N	0.339	0.24	None	gnomAD-3.1.2	3.95E-05	None	None	None	None	I	None	1.44837E-04	0	0	0	0	None	0	0	0	0	0
E/K	rs878877605	0.697	0.117	N	0.339	0.24	None	gnomAD-4.0.0	9.13528E-06	None	None	None	None	I	None	1.5731E-04	0	None	0	0	None	0	0	0	0	0
E/V	rs547188027	None	0.002	N	0.353	0.281	0.497871611283	gnomAD-4.0.0	1.56042E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.575E-05	0	3.66327E-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	0.1301	likely_benign	0.1236	benign	-0.187	Destabilizing	0.052	N	0.406	neutral	N	0.488441975	None	None	I
E/C	0.8136	likely_pathogenic	0.808	pathogenic	-0.052	Destabilizing	0.935	D	0.445	neutral	None	None	None	None	I
E/D	0.0825	likely_benign	0.0738	benign	-0.245	Destabilizing	None	N	0.182	neutral	N	0.491615566	None	None	I
E/F	0.681	likely_pathogenic	0.68	pathogenic	-0.133	Destabilizing	0.555	D	0.435	neutral	None	None	None	None	I
E/G	0.1251	likely_benign	0.1265	benign	-0.358	Destabilizing	0.117	N	0.462	neutral	N	0.500160479	None	None	I
E/H	0.4276	ambiguous	0.4282	ambiguous	0.224	Stabilizing	0.555	D	0.351	neutral	None	None	None	None	I
E/I	0.3244	likely_benign	0.3193	benign	0.22	Stabilizing	0.081	N	0.45	neutral	None	None	None	None	I
E/K	0.1543	likely_benign	0.1729	benign	0.373	Stabilizing	0.117	N	0.339	neutral	N	0.461716734	None	None	I
E/L	0.373	ambiguous	0.3648	ambiguous	0.22	Stabilizing	0.081	N	0.457	neutral	None	None	None	None	I
E/M	0.427	ambiguous	0.4358	ambiguous	0.161	Stabilizing	0.824	D	0.425	neutral	None	None	None	None	I
E/N	0.1596	likely_benign	0.1437	benign	0.144	Stabilizing	0.081	N	0.348	neutral	None	None	None	None	I
E/P	0.4021	ambiguous	0.3839	ambiguous	0.104	Stabilizing	None	N	0.179	neutral	None	None	None	None	I
E/Q	0.151	likely_benign	0.1547	benign	0.167	Stabilizing	0.117	N	0.351	neutral	N	0.496021309	None	None	I
E/R	0.2649	likely_benign	0.2913	benign	0.594	Stabilizing	0.38	N	0.353	neutral	None	None	None	None	I
E/S	0.1861	likely_benign	0.1765	benign	-0.029	Destabilizing	0.081	N	0.301	neutral	None	None	None	None	I
E/T	0.2009	likely_benign	0.1983	benign	0.11	Stabilizing	0.149	N	0.432	neutral	None	None	None	None	I
E/V	0.1758	likely_benign	0.1726	benign	0.104	Stabilizing	0.002	N	0.353	neutral	N	0.484825667	None	None	I
E/W	0.8454	likely_pathogenic	0.8558	pathogenic	-0.032	Destabilizing	0.935	D	0.503	neutral	None	None	None	None	I
E/Y	0.504	ambiguous	0.495	ambiguous	0.103	Stabilizing	0.791	D	0.438	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.