TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10066	30421;30422;30423	chr2:178704174;178704173;178704172	chr2:179568901;179568900;179568899
N2AB	9749	29470;29471;29472	chr2:178704174;178704173;178704172	chr2:179568901;179568900;179568899
N2A	8822	26689;26690;26691	chr2:178704174;178704173;178704172	chr2:179568901;179568900;179568899
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-85
• Domain position: 78
• Structural Position: 168
• Q(SASA): 0.4125
• 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/Q	rs370072382	-0.357	0.294	None	0.279	0.152	None	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	2.66E-05	0
E/Q	rs370072382	-0.357	0.294	None	0.279	0.152	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/Q	rs370072382	-0.357	0.294	None	0.279	0.152	None	gnomAD-4.0.0	6.94E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.23821E-05	1.09794E-05	3.20174E-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	0.1911	likely_benign	0.27	benign	-0.469	Destabilizing	0.014	N	0.357	neutral	None	None	None	None	N
E/C	0.9188	likely_pathogenic	0.9565	pathogenic	0.038	Stabilizing	0.998	D	0.691	prob.neutral	None	None	None	None	N
E/D	0.4212	ambiguous	0.6896	pathogenic	-0.499	Destabilizing	0.822	D	0.623	neutral	None	None	None	None	N
E/F	0.8377	likely_pathogenic	0.9181	pathogenic	-0.369	Destabilizing	0.978	D	0.691	prob.neutral	None	None	None	None	N
E/G	0.3472	ambiguous	0.5027	ambiguous	-0.705	Destabilizing	0.014	N	0.389	neutral	None	None	None	None	N
E/H	0.6042	likely_pathogenic	0.7717	pathogenic	-0.381	Destabilizing	0.978	D	0.641	neutral	None	None	None	None	N
E/I	0.452	ambiguous	0.5975	pathogenic	0.132	Stabilizing	0.956	D	0.698	prob.neutral	None	None	None	None	N
E/K	0.224	likely_benign	0.3471	ambiguous	0.219	Stabilizing	0.698	D	0.625	neutral	None	None	None	None	N
E/L	0.5432	ambiguous	0.7044	pathogenic	0.132	Stabilizing	0.956	D	0.666	neutral	None	None	None	None	N
E/M	0.5246	ambiguous	0.6554	pathogenic	0.395	Stabilizing	0.998	D	0.699	prob.neutral	None	None	None	None	N
E/N	0.5181	ambiguous	0.7401	pathogenic	-0.084	Destabilizing	0.956	D	0.635	neutral	None	None	None	None	N
E/P	0.9652	likely_pathogenic	0.9856	pathogenic	-0.047	Destabilizing	0.978	D	0.71	prob.delet.	None	None	None	None	N
E/Q	0.1492	likely_benign	0.1977	benign	-0.046	Destabilizing	0.294	N	0.279	neutral	None	None	None	None	N
E/R	0.3779	ambiguous	0.5336	ambiguous	0.357	Stabilizing	0.956	D	0.639	neutral	None	None	None	None	N
E/S	0.2984	likely_benign	0.4306	ambiguous	-0.276	Destabilizing	0.754	D	0.618	neutral	None	None	None	None	N
E/T	0.2829	likely_benign	0.3995	ambiguous	-0.086	Destabilizing	0.86	D	0.662	neutral	None	None	None	None	N
E/V	0.2572	likely_benign	0.369	ambiguous	-0.047	Destabilizing	0.89	D	0.671	neutral	None	None	None	None	N
E/W	0.9461	likely_pathogenic	0.9756	pathogenic	-0.219	Destabilizing	0.998	D	0.69	prob.neutral	None	None	None	None	N
E/Y	0.7891	likely_pathogenic	0.8939	pathogenic	-0.121	Destabilizing	0.993	D	0.701	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.