TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6781	20566;20567;20568	chr2:178725981;178725980;178725979	chr2:179590708;179590707;179590706
N2AB	6464	19615;19616;19617	chr2:178725981;178725980;178725979	chr2:179590708;179590707;179590706
N2A	5537	16834;16835;16836	chr2:178725981;178725980;178725979	chr2:179590708;179590707;179590706
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: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-52
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.5754
• 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/A	None	None	0.917	N	0.55	0.413	0.555867075214	gnomAD-4.0.0	3.20496E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.75738E-06	0	0
E/K	rs72648958	-0.258	0.953	D	0.553	0.318	None	gnomAD-2.1.1	9.93871E-04	None	None	None	None	N	None	3.33417E-04	2.61203E-04	None	0	0	None	9.65894E-04	None	4.01994E-04	1.66299E-03	1.14384E-03
E/K	rs72648958	-0.258	0.953	D	0.553	0.318	None	gnomAD-3.1.2	1.16377E-03	None	None	None	None	N	None	4.58738E-04	1.96747E-04	0	0	0	None	2.82539E-04	0	2.19098E-03	6.20091E-04	0
E/K	rs72648958	-0.258	0.953	D	0.553	0.318	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	1E-03	None	None	None	0	None
E/K	rs72648958	-0.258	0.953	D	0.553	0.318	None	gnomAD-4.0.0	2.09579E-03	None	None	None	None	N	None	4.14361E-04	2.18539E-04	None	3.39859E-05	0	None	5.32265E-04	9.94695E-04	2.61858E-03	1.07804E-03	1.71788E-03
E/Q	rs72648958	-0.495	0.99	N	0.571	0.259	0.303781844768	gnomAD-2.1.1	4.08E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.97E-06	0
E/Q	rs72648958	-0.495	0.99	N	0.571	0.259	0.303781844768	gnomAD-4.0.0	1.37384E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80409E-06	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	0.1653	likely_benign	0.152	benign	-0.565	Destabilizing	0.917	D	0.55	neutral	N	0.501723578	None	None	N
E/C	0.8645	likely_pathogenic	0.8586	pathogenic	-0.284	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
E/D	0.1961	likely_benign	0.1614	benign	-0.995	Destabilizing	0.415	N	0.541	neutral	D	0.537273285	None	None	N
E/F	0.72	likely_pathogenic	0.6891	pathogenic	-0.499	Destabilizing	0.995	D	0.735	prob.delet.	None	None	None	None	N
E/G	0.2234	likely_benign	0.2039	benign	-0.88	Destabilizing	0.103	N	0.419	neutral	N	0.510650801	None	None	N
E/H	0.4348	ambiguous	0.3946	ambiguous	-0.969	Destabilizing	0.123	N	0.397	neutral	None	None	None	None	N
E/I	0.3286	likely_benign	0.3146	benign	0.273	Stabilizing	0.996	D	0.727	prob.delet.	None	None	None	None	N
E/K	0.1937	likely_benign	0.1773	benign	-0.77	Destabilizing	0.953	D	0.553	neutral	D	0.532000751	None	None	N
E/L	0.3964	ambiguous	0.3777	ambiguous	0.273	Stabilizing	0.989	D	0.679	prob.neutral	None	None	None	None	N
E/M	0.4811	ambiguous	0.4616	ambiguous	0.751	Stabilizing	0.995	D	0.711	prob.delet.	None	None	None	None	N
E/N	0.3179	likely_benign	0.268	benign	-0.92	Destabilizing	0.073	N	0.445	neutral	None	None	None	None	N
E/P	0.8501	likely_pathogenic	0.8197	pathogenic	0.015	Stabilizing	0.976	D	0.657	neutral	None	None	None	None	N
E/Q	0.1192	likely_benign	0.1089	benign	-0.802	Destabilizing	0.99	D	0.571	neutral	N	0.491674282	None	None	N
E/R	0.3053	likely_benign	0.2811	benign	-0.654	Destabilizing	0.995	D	0.562	neutral	None	None	None	None	N
E/S	0.216	likely_benign	0.1879	benign	-1.224	Destabilizing	0.936	D	0.526	neutral	None	None	None	None	N
E/T	0.2152	likely_benign	0.1918	benign	-0.985	Destabilizing	0.953	D	0.588	neutral	None	None	None	None	N
E/V	0.1987	likely_benign	0.1905	benign	0.015	Stabilizing	0.993	D	0.66	neutral	N	0.494610461	None	None	N
E/W	0.9076	likely_pathogenic	0.8923	pathogenic	-0.501	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
E/Y	0.6381	likely_pathogenic	0.6022	pathogenic	-0.35	Destabilizing	0.996	D	0.705	prob.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.