TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6622	20089;20090;20091	chr2:178727714;178727713;178727712	chr2:179592441;179592440;179592439
N2AB	6305	19138;19139;19140	chr2:178727714;178727713;178727712	chr2:179592441;179592440;179592439
N2A	5378	16357;16358;16359	chr2:178727714;178727713;178727712	chr2:179592441;179592440;179592439
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-50
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.2371
• 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
I/F	rs775092361	-1.044	0.006	N	0.218	0.322	0.292423486923	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	5.56E-05	None	0	None	0	0	0
I/N	rs1413452032	-1.391	0.927	N	0.626	0.544	0.822951172334	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
I/N	rs1413452032	-1.391	0.927	N	0.626	0.544	0.822951172334	gnomAD-4.0.0	1.59231E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86072E-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
I/A	0.222	likely_benign	0.1918	benign	-1.898	Destabilizing	0.013	N	0.216	neutral	None	None	None	None	I
I/C	0.7687	likely_pathogenic	0.6674	pathogenic	-1.072	Destabilizing	0.981	D	0.529	neutral	None	None	None	None	I
I/D	0.8752	likely_pathogenic	0.809	pathogenic	-1.384	Destabilizing	0.828	D	0.637	neutral	None	None	None	None	I
I/E	0.7157	likely_pathogenic	0.6495	pathogenic	-1.205	Destabilizing	0.828	D	0.595	neutral	None	None	None	None	I
I/F	0.1398	likely_benign	0.106	benign	-0.993	Destabilizing	0.006	N	0.218	neutral	N	0.503649362	None	None	I
I/G	0.7156	likely_pathogenic	0.6262	pathogenic	-2.402	Highly Destabilizing	0.704	D	0.522	neutral	None	None	None	None	I
I/H	0.6049	likely_pathogenic	0.5017	ambiguous	-1.762	Destabilizing	0.981	D	0.577	neutral	None	None	None	None	I
I/K	0.5342	ambiguous	0.4743	ambiguous	-1.123	Destabilizing	0.704	D	0.587	neutral	None	None	None	None	I
I/L	0.1123	likely_benign	0.1017	benign	-0.486	Destabilizing	0.002	N	0.113	neutral	D	0.531731393	None	None	I
I/M	0.0952	likely_benign	0.0938	benign	-0.442	Destabilizing	0.139	N	0.24	neutral	N	0.513991709	None	None	I
I/N	0.5268	ambiguous	0.4221	ambiguous	-1.248	Destabilizing	0.927	D	0.626	neutral	N	0.520565529	None	None	I
I/P	0.7741	likely_pathogenic	0.7107	pathogenic	-0.932	Destabilizing	0.944	D	0.623	neutral	None	None	None	None	I
I/Q	0.5526	ambiguous	0.4711	ambiguous	-1.152	Destabilizing	0.944	D	0.609	neutral	None	None	None	None	I
I/R	0.3781	ambiguous	0.3144	benign	-0.918	Destabilizing	0.944	D	0.625	neutral	None	None	None	None	I
I/S	0.2912	likely_benign	0.2362	benign	-2.032	Highly Destabilizing	0.27	N	0.415	neutral	N	0.503017478	None	None	I
I/T	0.1036	likely_benign	0.0917	benign	-1.707	Destabilizing	0.01	N	0.213	neutral	N	0.486052086	None	None	I
I/V	0.0854	likely_benign	0.079	benign	-0.932	Destabilizing	0.139	N	0.237	neutral	N	0.492247498	None	None	I
I/W	0.7323	likely_pathogenic	0.6263	pathogenic	-1.278	Destabilizing	0.995	D	0.589	neutral	None	None	None	None	I
I/Y	0.561	ambiguous	0.4651	ambiguous	-0.956	Destabilizing	0.543	D	0.583	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.