TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18659	56200;56201;56202	chr2:178600929;178600928;178600927	chr2:179465656;179465655;179465654
N2AB	17018	51277;51278;51279	chr2:178600929;178600928;178600927	chr2:179465656;179465655;179465654
N2A	16091	48496;48497;48498	chr2:178600929;178600928;178600927	chr2:179465656;179465655;179465654
N2B	9594	29005;29006;29007	chr2:178600929;178600928;178600927	chr2:179465656;179465655;179465654
Novex-1	9719	29380;29381;29382	chr2:178600929;178600928;178600927	chr2:179465656;179465655;179465654
Novex-2	9786	29581;29582;29583	chr2:178600929;178600928;178600927	chr2:179465656;179465655;179465654
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: Fn3-23
• Domain position: 81
• Structural Position: 108
• Q(SASA): 0.0819
• 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	None	None	0.767	N	0.331	0.301	0.549460442827	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	0.8022	likely_pathogenic	0.8111	pathogenic	-2.486	Highly Destabilizing	0.998	D	0.668	neutral	D	0.550010679	None	None	N
V/C	0.9469	likely_pathogenic	0.9465	pathogenic	-1.993	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
V/D	0.9984	likely_pathogenic	0.9988	pathogenic	-3.585	Highly Destabilizing	1.0	D	0.893	deleterious	D	0.629947995	None	None	N
V/E	0.9944	likely_pathogenic	0.9956	pathogenic	-3.292	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
V/F	0.9696	likely_pathogenic	0.9633	pathogenic	-1.452	Destabilizing	0.999	D	0.852	deleterious	D	0.56795035	None	None	N
V/G	0.8985	likely_pathogenic	0.9228	pathogenic	-3.056	Highly Destabilizing	1.0	D	0.894	deleterious	D	0.629947995	None	None	N
V/H	0.9992	likely_pathogenic	0.9991	pathogenic	-2.948	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/I	0.1725	likely_benign	0.1333	benign	-0.828	Destabilizing	0.767	D	0.331	neutral	N	0.510494903	None	None	N
V/K	0.9972	likely_pathogenic	0.9976	pathogenic	-2.157	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
V/L	0.8447	likely_pathogenic	0.7965	pathogenic	-0.828	Destabilizing	0.981	D	0.627	neutral	N	0.504973397	None	None	N
V/M	0.9053	likely_pathogenic	0.8727	pathogenic	-1.035	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
V/N	0.9938	likely_pathogenic	0.9945	pathogenic	-2.776	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
V/P	0.9954	likely_pathogenic	0.9968	pathogenic	-1.363	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
V/Q	0.9946	likely_pathogenic	0.9949	pathogenic	-2.473	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
V/R	0.9925	likely_pathogenic	0.9939	pathogenic	-2.102	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
V/S	0.9605	likely_pathogenic	0.9645	pathogenic	-3.264	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
V/T	0.9222	likely_pathogenic	0.9266	pathogenic	-2.829	Highly Destabilizing	0.998	D	0.743	deleterious	None	None	None	None	N
V/W	0.9995	likely_pathogenic	0.9994	pathogenic	-2.093	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/Y	0.9969	likely_pathogenic	0.9966	pathogenic	-1.773	Destabilizing	1.0	D	0.853	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.