TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21758	65497;65498;65499	chr2:178584279;178584278;178584277	chr2:179449006;179449005;179449004
N2AB	20117	60574;60575;60576	chr2:178584279;178584278;178584277	chr2:179449006;179449005;179449004
N2A	19190	57793;57794;57795	chr2:178584279;178584278;178584277	chr2:179449006;179449005;179449004
N2B	12693	38302;38303;38304	chr2:178584279;178584278;178584277	chr2:179449006;179449005;179449004
Novex-1	12818	38677;38678;38679	chr2:178584279;178584278;178584277	chr2:179449006;179449005;179449004
Novex-2	12885	38878;38879;38880	chr2:178584279;178584278;178584277	chr2:179449006;179449005;179449004
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-46
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.0925
• 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	0.856	N	0.549	0.256	0.437207349437	gnomAD-4.0.0	1.76645E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.12533E-06	0	0
V/F	rs1394549346	None	0.954	N	0.82	0.297	0.431822907236	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/F	rs1394549346	None	0.954	N	0.82	0.297	0.431822907236	gnomAD-4.0.0	1.93389E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.69733E-07	2.47488E-05	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	0.5853	likely_pathogenic	0.4553	ambiguous	-1.558	Destabilizing	0.856	D	0.549	neutral	N	0.512542625	None	None	N
V/C	0.8663	likely_pathogenic	0.8204	pathogenic	-1.325	Destabilizing	0.998	D	0.801	deleterious	None	None	None	None	N
V/D	0.9907	likely_pathogenic	0.9804	pathogenic	-2.46	Highly Destabilizing	0.992	D	0.804	deleterious	N	0.482406965	None	None	N
V/E	0.9772	likely_pathogenic	0.9583	pathogenic	-2.451	Highly Destabilizing	0.994	D	0.82	deleterious	None	None	None	None	N
V/F	0.8788	likely_pathogenic	0.7991	pathogenic	-1.298	Destabilizing	0.954	D	0.82	deleterious	N	0.495517089	None	None	N
V/G	0.8639	likely_pathogenic	0.7832	pathogenic	-1.878	Destabilizing	0.977	D	0.817	deleterious	N	0.482153475	None	None	N
V/H	0.995	likely_pathogenic	0.9889	pathogenic	-1.492	Destabilizing	0.998	D	0.814	deleterious	None	None	None	None	N
V/I	0.1232	likely_benign	0.1179	benign	-0.754	Destabilizing	0.018	N	0.261	neutral	N	0.467559697	None	None	N
V/K	0.9886	likely_pathogenic	0.9764	pathogenic	-1.329	Destabilizing	0.982	D	0.823	deleterious	None	None	None	None	N
V/L	0.6959	likely_pathogenic	0.633	pathogenic	-0.754	Destabilizing	0.297	N	0.517	neutral	N	0.481086355	None	None	N
V/M	0.6252	likely_pathogenic	0.5385	ambiguous	-0.614	Destabilizing	0.965	D	0.731	deleterious	None	None	None	None	N
V/N	0.9656	likely_pathogenic	0.9434	pathogenic	-1.298	Destabilizing	0.994	D	0.805	deleterious	None	None	None	None	N
V/P	0.8856	likely_pathogenic	0.7797	pathogenic	-0.991	Destabilizing	0.994	D	0.825	deleterious	None	None	None	None	N
V/Q	0.9749	likely_pathogenic	0.9549	pathogenic	-1.508	Destabilizing	0.994	D	0.829	deleterious	None	None	None	None	N
V/R	0.9765	likely_pathogenic	0.9566	pathogenic	-0.833	Destabilizing	0.994	D	0.803	deleterious	None	None	None	None	N
V/S	0.8291	likely_pathogenic	0.745	pathogenic	-1.692	Destabilizing	0.982	D	0.825	deleterious	None	None	None	None	N
V/T	0.608	likely_pathogenic	0.5105	ambiguous	-1.584	Destabilizing	0.887	D	0.661	prob.neutral	None	None	None	None	N
V/W	0.9968	likely_pathogenic	0.9925	pathogenic	-1.578	Destabilizing	0.998	D	0.833	deleterious	None	None	None	None	N
V/Y	0.9887	likely_pathogenic	0.9777	pathogenic	-1.263	Destabilizing	0.982	D	0.816	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.