TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19744	59455;59456;59457	chr2:178592889;178592888;178592887	chr2:179457616;179457615;179457614
N2AB	18103	54532;54533;54534	chr2:178592889;178592888;178592887	chr2:179457616;179457615;179457614
N2A	17176	51751;51752;51753	chr2:178592889;178592888;178592887	chr2:179457616;179457615;179457614
N2B	10679	32260;32261;32262	chr2:178592889;178592888;178592887	chr2:179457616;179457615;179457614
Novex-1	10804	32635;32636;32637	chr2:178592889;178592888;178592887	chr2:179457616;179457615;179457614
Novex-2	10871	32836;32837;32838	chr2:178592889;178592888;178592887	chr2:179457616;179457615;179457614
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-31
• Domain position: 65
• Structural Position: 93
• Q(SASA): 0.1064
• 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/A	None	None	0.989	N	0.661	0.391	0.597208634801	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.6931	likely_pathogenic	0.6479	pathogenic	-1.602	Destabilizing	0.989	D	0.661	neutral	N	0.478822113	None	None	N
V/C	0.942	likely_pathogenic	0.9361	pathogenic	-1.143	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
V/D	0.9943	likely_pathogenic	0.9913	pathogenic	-2.351	Highly Destabilizing	0.999	D	0.849	deleterious	N	0.492153428	None	None	N
V/E	0.9789	likely_pathogenic	0.9711	pathogenic	-2.037	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
V/F	0.8287	likely_pathogenic	0.7726	pathogenic	-0.879	Destabilizing	0.997	D	0.795	deleterious	N	0.507215809	None	None	N
V/G	0.8989	likely_pathogenic	0.8679	pathogenic	-2.213	Highly Destabilizing	0.998	D	0.861	deleterious	D	0.522374457	None	None	N
V/H	0.9952	likely_pathogenic	0.993	pathogenic	-2.265	Highly Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
V/I	0.1009	likely_benign	0.1055	benign	0.152	Stabilizing	0.543	D	0.255	neutral	N	0.508651384	None	None	N
V/K	0.9868	likely_pathogenic	0.9826	pathogenic	-1.167	Destabilizing	0.999	D	0.834	deleterious	None	None	None	None	N
V/L	0.5933	likely_pathogenic	0.5861	pathogenic	0.152	Stabilizing	0.948	D	0.419	neutral	N	0.491446916	None	None	N
V/M	0.5791	likely_pathogenic	0.5249	ambiguous	-0.12	Destabilizing	0.96	D	0.493	neutral	None	None	None	None	N
V/N	0.982	likely_pathogenic	0.9763	pathogenic	-1.774	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
V/P	0.9875	likely_pathogenic	0.9845	pathogenic	-0.41	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
V/Q	0.9796	likely_pathogenic	0.9727	pathogenic	-1.389	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
V/R	0.9828	likely_pathogenic	0.9771	pathogenic	-1.51	Destabilizing	0.999	D	0.852	deleterious	None	None	None	None	N
V/S	0.9477	likely_pathogenic	0.9338	pathogenic	-2.344	Highly Destabilizing	0.999	D	0.828	deleterious	None	None	None	None	N
V/T	0.8769	likely_pathogenic	0.8671	pathogenic	-1.849	Destabilizing	0.996	D	0.679	prob.neutral	None	None	None	None	N
V/W	0.997	likely_pathogenic	0.995	pathogenic	-1.423	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
V/Y	0.9823	likely_pathogenic	0.973	pathogenic	-0.973	Destabilizing	1.0	D	0.773	deleterious	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.