TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19598	59017;59018;59019	chr2:178593416;178593415;178593414	chr2:179458143;179458142;179458141
N2AB	17957	54094;54095;54096	chr2:178593416;178593415;178593414	chr2:179458143;179458142;179458141
N2A	17030	51313;51314;51315	chr2:178593416;178593415;178593414	chr2:179458143;179458142;179458141
N2B	10533	31822;31823;31824	chr2:178593416;178593415;178593414	chr2:179458143;179458142;179458141
Novex-1	10658	32197;32198;32199	chr2:178593416;178593415;178593414	chr2:179458143;179458142;179458141
Novex-2	10725	32398;32399;32400	chr2:178593416;178593415;178593414	chr2:179458143;179458142;179458141
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-30
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.115
• 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
V/I	rs1375428423	None	0.198	N	0.159	0.174	0.315314060047	gnomAD-4.0.0	1.59235E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85972E-06	0	0
V/L	rs1375428423	None	0.9	N	0.379	0.224	0.297031009988	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	2.94E-05	0	0
V/L	rs1375428423	None	0.9	N	0.379	0.224	0.297031009988	gnomAD-4.0.0	6.40953E-06	None	None	None	None	N	None	0	1.69612E-05	None	0	0	None	0	0	9.57685E-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
V/A	0.8548	likely_pathogenic	0.8823	pathogenic	-2.056	Highly Destabilizing	0.948	D	0.656	neutral	N	0.49106011	None	None	N
V/C	0.9476	likely_pathogenic	0.961	pathogenic	-1.196	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
V/D	0.9987	likely_pathogenic	0.9992	pathogenic	-3.0	Highly Destabilizing	0.999	D	0.895	deleterious	None	None	None	None	N
V/E	0.9952	likely_pathogenic	0.9965	pathogenic	-2.666	Highly Destabilizing	0.999	D	0.857	deleterious	D	0.526054079	None	None	N
V/F	0.9085	likely_pathogenic	0.9208	pathogenic	-1.139	Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	N
V/G	0.9481	likely_pathogenic	0.9589	pathogenic	-2.672	Highly Destabilizing	0.999	D	0.877	deleterious	N	0.514533189	None	None	N
V/H	0.9984	likely_pathogenic	0.9988	pathogenic	-2.718	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/I	0.0937	likely_benign	0.1004	benign	-0.257	Destabilizing	0.198	N	0.159	neutral	N	0.452293882	None	None	N
V/K	0.9966	likely_pathogenic	0.9976	pathogenic	-1.549	Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
V/L	0.3498	ambiguous	0.4076	ambiguous	-0.257	Destabilizing	0.9	D	0.379	neutral	N	0.392330354	None	None	N
V/M	0.7438	likely_pathogenic	0.7763	pathogenic	-0.451	Destabilizing	0.998	D	0.623	neutral	None	None	None	None	N
V/N	0.9955	likely_pathogenic	0.9969	pathogenic	-2.295	Highly Destabilizing	0.999	D	0.903	deleterious	None	None	None	None	N
V/P	0.9936	likely_pathogenic	0.995	pathogenic	-0.839	Destabilizing	0.999	D	0.86	deleterious	None	None	None	None	N
V/Q	0.9942	likely_pathogenic	0.9958	pathogenic	-1.871	Destabilizing	0.999	D	0.878	deleterious	None	None	None	None	N
V/R	0.9937	likely_pathogenic	0.9953	pathogenic	-1.833	Destabilizing	0.999	D	0.904	deleterious	None	None	None	None	N
V/S	0.981	likely_pathogenic	0.9862	pathogenic	-2.737	Highly Destabilizing	0.999	D	0.818	deleterious	None	None	None	None	N
V/T	0.9349	likely_pathogenic	0.9503	pathogenic	-2.238	Highly Destabilizing	0.992	D	0.639	neutral	None	None	None	None	N
V/W	0.9989	likely_pathogenic	0.9992	pathogenic	-1.719	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
V/Y	0.9939	likely_pathogenic	0.9949	pathogenic	-1.358	Destabilizing	0.999	D	0.703	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.