TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16963	51112;51113;51114	chr2:178611242;178611241;178611240	chr2:179475969;179475968;179475967
N2AB	15322	46189;46190;46191	chr2:178611242;178611241;178611240	chr2:179475969;179475968;179475967
N2A	14395	43408;43409;43410	chr2:178611242;178611241;178611240	chr2:179475969;179475968;179475967
N2B	7898	23917;23918;23919	chr2:178611242;178611241;178611240	chr2:179475969;179475968;179475967
Novex-1	8023	24292;24293;24294	chr2:178611242;178611241;178611240	chr2:179475969;179475968;179475967
Novex-2	8090	24493;24494;24495	chr2:178611242;178611241;178611240	chr2:179475969;179475968;179475967
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-111
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5246
• 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
D/E	None	None	1.0	N	0.406	0.246	0.19670166235	gnomAD-4.0.0	2.05424E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69964E-06	0	0
D/N	rs760115243	-0.592	1.0	N	0.617	0.362	0.259761712551	gnomAD-2.1.1	4.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
D/N	rs760115243	-0.592	1.0	N	0.617	0.362	0.259761712551	gnomAD-4.0.0	1.36954E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.32089E-05	0
D/V	rs775055815	0.257	1.0	D	0.693	0.591	0.411133732114	gnomAD-2.1.1	4.04E-05	None	None	None	None	I	None	0	0	None	0	0	None	3.27354E-04	None	0	0	0
D/V	rs775055815	0.257	1.0	D	0.693	0.591	0.411133732114	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	4.14422E-04	0
D/V	rs775055815	0.257	1.0	D	0.693	0.591	0.411133732114	gnomAD-4.0.0	1.30245E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.30713E-04	0
D/Y	rs760115243	-0.064	1.0	D	0.645	0.538	0.396794106654	gnomAD-2.1.1	4.05E-05	None	None	None	None	I	None	0	0	None	0	0	None	3.27354E-04	None	0	0	0
D/Y	rs760115243	-0.064	1.0	D	0.645	0.538	0.396794106654	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	4.14766E-04	0
D/Y	rs760115243	-0.064	1.0	D	0.645	0.538	0.396794106654	gnomAD-4.0.0	1.36453E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.30784E-04	1.60339E-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
D/A	0.495	ambiguous	0.5078	ambiguous	-0.398	Destabilizing	1.0	D	0.69	prob.neutral	D	0.522977177	None	None	I
D/C	0.8667	likely_pathogenic	0.8742	pathogenic	-0.168	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	I
D/E	0.3327	likely_benign	0.3356	benign	-0.474	Destabilizing	1.0	D	0.406	neutral	N	0.452627178	None	None	I
D/F	0.8928	likely_pathogenic	0.901	pathogenic	-0.113	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	I
D/G	0.4145	ambiguous	0.4174	ambiguous	-0.681	Destabilizing	1.0	D	0.701	prob.neutral	N	0.444799208	None	None	I
D/H	0.5411	ambiguous	0.5362	ambiguous	-0.261	Destabilizing	1.0	D	0.635	neutral	D	0.524849289	None	None	I
D/I	0.7836	likely_pathogenic	0.8022	pathogenic	0.324	Stabilizing	1.0	D	0.674	neutral	None	None	None	None	I
D/K	0.7198	likely_pathogenic	0.7319	pathogenic	-0.195	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	I
D/L	0.7951	likely_pathogenic	0.807	pathogenic	0.324	Stabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	I
D/M	0.8926	likely_pathogenic	0.9011	pathogenic	0.559	Stabilizing	1.0	D	0.665	neutral	None	None	None	None	I
D/N	0.1442	likely_benign	0.1464	benign	-0.534	Destabilizing	1.0	D	0.617	neutral	N	0.450500423	None	None	I
D/P	0.9137	likely_pathogenic	0.9333	pathogenic	0.108	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
D/Q	0.63	likely_pathogenic	0.6379	pathogenic	-0.432	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
D/R	0.7449	likely_pathogenic	0.7536	pathogenic	0.01	Stabilizing	1.0	D	0.665	neutral	None	None	None	None	I
D/S	0.2554	likely_benign	0.2675	benign	-0.7	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	I
D/T	0.5114	ambiguous	0.5191	ambiguous	-0.478	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
D/V	0.605	likely_pathogenic	0.6165	pathogenic	0.108	Stabilizing	1.0	D	0.693	prob.neutral	D	0.595551048	None	None	I
D/W	0.9723	likely_pathogenic	0.9754	pathogenic	0.043	Stabilizing	1.0	D	0.667	neutral	None	None	None	None	I
D/Y	0.5534	ambiguous	0.5685	pathogenic	0.105	Stabilizing	1.0	D	0.645	neutral	D	0.574412569	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.