TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14417	43474;43475;43476	chr2:178632757;178632756;178632755	chr2:179497484;179497483;179497482
N2AB	12776	38551;38552;38553	chr2:178632757;178632756;178632755	chr2:179497484;179497483;179497482
N2A	11849	35770;35771;35772	chr2:178632757;178632756;178632755	chr2:179497484;179497483;179497482
N2B	5352	16279;16280;16281	chr2:178632757;178632756;178632755	chr2:179497484;179497483;179497482
Novex-1	5477	16654;16655;16656	chr2:178632757;178632756;178632755	chr2:179497484;179497483;179497482
Novex-2	5544	16855;16856;16857	chr2:178632757;178632756;178632755	chr2:179497484;179497483;179497482
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: Ig-95
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.2573
• 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	rs906675886	-0.129	0.997	N	0.504	0.295	None	gnomAD-2.1.1	8.08E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
V/I	rs906675886	-0.129	0.997	N	0.504	0.295	None	gnomAD-4.0.0	1.02676E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.34948E-05	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	0.4573	ambiguous	0.4108	ambiguous	-1.441	Destabilizing	0.999	D	0.512	neutral	D	0.544855455	None	None	N
V/C	0.8739	likely_pathogenic	0.8446	pathogenic	-0.874	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
V/D	0.7885	likely_pathogenic	0.7705	pathogenic	-1.237	Destabilizing	1.0	D	0.807	deleterious	D	0.671955884	None	None	N
V/E	0.572	likely_pathogenic	0.5676	pathogenic	-1.128	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
V/F	0.3773	ambiguous	0.3738	ambiguous	-0.887	Destabilizing	1.0	D	0.779	deleterious	D	0.607942725	None	None	N
V/G	0.595	likely_pathogenic	0.5678	pathogenic	-1.868	Destabilizing	1.0	D	0.783	deleterious	D	0.671239507	None	None	N
V/H	0.8465	likely_pathogenic	0.8307	pathogenic	-1.476	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
V/I	0.0738	likely_benign	0.0738	benign	-0.322	Destabilizing	0.997	D	0.504	neutral	N	0.51897943	None	None	N
V/K	0.5384	ambiguous	0.5376	ambiguous	-1.094	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
V/L	0.3705	ambiguous	0.35	ambiguous	-0.322	Destabilizing	0.997	D	0.522	neutral	N	0.516140575	None	None	N
V/M	0.2191	likely_benign	0.2081	benign	-0.261	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
V/N	0.6195	likely_pathogenic	0.5843	pathogenic	-1.117	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
V/P	0.9727	likely_pathogenic	0.9759	pathogenic	-0.661	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
V/Q	0.55	ambiguous	0.5372	ambiguous	-1.102	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
V/R	0.5069	ambiguous	0.4892	ambiguous	-0.817	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
V/S	0.5603	ambiguous	0.5176	ambiguous	-1.739	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
V/T	0.3657	ambiguous	0.3364	benign	-1.499	Destabilizing	0.999	D	0.57	neutral	None	None	None	None	N
V/W	0.9482	likely_pathogenic	0.9472	pathogenic	-1.247	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
V/Y	0.8082	likely_pathogenic	0.8044	pathogenic	-0.847	Destabilizing	1.0	D	0.783	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.