TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4777	14554;14555;14556	chr2:178738124;178738123;178738122	chr2:179602851;179602850;179602849
N2AB	4460	13603;13604;13605	chr2:178738124;178738123;178738122	chr2:179602851;179602850;179602849
N2A	3533	10822;10823;10824	chr2:178738124;178738123;178738122	chr2:179602851;179602850;179602849
N2B	4414	13465;13466;13467	chr2:178738124;178738123;178738122	chr2:179602851;179602850;179602849
Novex-1	4539	13840;13841;13842	chr2:178738124;178738123;178738122	chr2:179602851;179602850;179602849
Novex-2	4606	14041;14042;14043	chr2:178738124;178738123;178738122	chr2:179602851;179602850;179602849
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-30
• Domain position: 78
• Structural Position: 162
• Q(SASA): 0.8737
• 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/A	rs747457945	0.107	0.425	N	0.329	0.256	None	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	1.78E-05	0
E/A	rs747457945	0.107	0.425	N	0.329	0.256	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	7.23E-05	0	0	0	0	None	0	0	0	0	0
E/A	rs747457945	0.107	0.425	N	0.329	0.256	None	gnomAD-4.0.0	2.35483E-05	None	None	None	None	I	None	4.00352E-05	0	None	0	0	None	0	0	2.88192E-05	0	1.60123E-05
E/K	rs1405978578	0.652	0.27	N	0.269	0.26	0.276898752692	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
E/K	rs1405978578	0.652	0.27	N	0.269	0.26	0.276898752692	gnomAD-4.0.0	1.59146E-06	None	None	None	None	I	None	5.65547E-05	0	None	0	0	None	0	0	0	0	0
E/V	None	None	0.784	N	0.358	0.35	0.448498829774	gnomAD-4.0.0	6.84233E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99493E-07	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
E/A	0.1591	likely_benign	0.1691	benign	-0.409	Destabilizing	0.425	N	0.329	neutral	N	0.44464574	None	None	I
E/C	0.8939	likely_pathogenic	0.9111	pathogenic	-0.254	Destabilizing	0.995	D	0.239	neutral	None	None	None	None	I
E/D	0.189	likely_benign	0.2014	benign	-0.375	Destabilizing	0.425	N	0.341	neutral	N	0.445100545	None	None	I
E/F	0.8176	likely_pathogenic	0.8439	pathogenic	-0.12	Destabilizing	0.981	D	0.263	neutral	None	None	None	None	I
E/G	0.2345	likely_benign	0.2668	benign	-0.618	Destabilizing	0.425	N	0.297	neutral	N	0.445100545	None	None	I
E/H	0.5628	ambiguous	0.5913	pathogenic	0.284	Stabilizing	0.944	D	0.247	neutral	None	None	None	None	I
E/I	0.347	ambiguous	0.3883	ambiguous	0.116	Stabilizing	0.944	D	0.293	neutral	None	None	None	None	I
E/K	0.1416	likely_benign	0.163	benign	0.249	Stabilizing	0.27	N	0.269	neutral	N	0.418993602	None	None	I
E/L	0.4666	ambiguous	0.4979	ambiguous	0.116	Stabilizing	0.704	D	0.328	neutral	None	None	None	None	I
E/M	0.4867	ambiguous	0.5269	ambiguous	0.08	Stabilizing	0.944	D	0.289	neutral	None	None	None	None	I
E/N	0.3483	ambiguous	0.3689	ambiguous	-0.206	Destabilizing	0.704	D	0.281	neutral	None	None	None	None	I
E/P	0.5022	ambiguous	0.5149	ambiguous	-0.039	Destabilizing	0.003	N	0.153	neutral	None	None	None	None	I
E/Q	0.1522	likely_benign	0.1588	benign	-0.133	Destabilizing	0.003	N	0.155	neutral	N	0.419722719	None	None	I
E/R	0.2518	likely_benign	0.2784	benign	0.579	Stabilizing	0.007	N	0.207	neutral	None	None	None	None	I
E/S	0.248	likely_benign	0.2679	benign	-0.358	Destabilizing	0.495	N	0.295	neutral	None	None	None	None	I
E/T	0.2421	likely_benign	0.2695	benign	-0.174	Destabilizing	0.704	D	0.325	neutral	None	None	None	None	I
E/V	0.2357	likely_benign	0.2636	benign	-0.039	Destabilizing	0.784	D	0.358	neutral	N	0.445521426	None	None	I
E/W	0.9354	likely_pathogenic	0.947	pathogenic	0.083	Stabilizing	0.995	D	0.251	neutral	None	None	None	None	I
E/Y	0.6953	likely_pathogenic	0.7354	pathogenic	0.137	Stabilizing	0.981	D	0.299	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.