TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18322	55189;55190;55191	chr2:178602438;178602437;178602436	chr2:179467165;179467164;179467163
N2AB	16681	50266;50267;50268	chr2:178602438;178602437;178602436	chr2:179467165;179467164;179467163
N2A	15754	47485;47486;47487	chr2:178602438;178602437;178602436	chr2:179467165;179467164;179467163
N2B	9257	27994;27995;27996	chr2:178602438;178602437;178602436	chr2:179467165;179467164;179467163
Novex-1	9382	28369;28370;28371	chr2:178602438;178602437;178602436	chr2:179467165;179467164;179467163
Novex-2	9449	28570;28571;28572	chr2:178602438;178602437;178602436	chr2:179467165;179467164;179467163
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: Fn3-21
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.3177
• 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	0.987	N	0.443	0.173	0.348764635752	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25001E-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	0.4205	ambiguous	0.2781	benign	-1.301	Destabilizing	0.543	D	0.265	neutral	N	0.484379297	None	None	N
V/C	0.7459	likely_pathogenic	0.6745	pathogenic	-0.86	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
V/D	0.9069	likely_pathogenic	0.8209	pathogenic	-1.181	Destabilizing	0.999	D	0.806	deleterious	None	None	None	None	N
V/E	0.8054	likely_pathogenic	0.7137	pathogenic	-1.204	Destabilizing	0.998	D	0.763	deleterious	N	0.4697119	None	None	N
V/F	0.4006	ambiguous	0.3286	benign	-1.086	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
V/G	0.5281	ambiguous	0.3696	ambiguous	-1.589	Destabilizing	0.997	D	0.707	prob.neutral	N	0.479132876	None	None	N
V/H	0.9216	likely_pathogenic	0.8777	pathogenic	-1.167	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
V/I	0.0886	likely_benign	0.0847	benign	-0.627	Destabilizing	0.987	D	0.443	neutral	N	0.481626993	None	None	N
V/K	0.8462	likely_pathogenic	0.7924	pathogenic	-1.22	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
V/L	0.4073	ambiguous	0.3403	ambiguous	-0.627	Destabilizing	0.973	D	0.441	neutral	N	0.487206171	None	None	N
V/M	0.3426	ambiguous	0.2817	benign	-0.464	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
V/N	0.8008	likely_pathogenic	0.688	pathogenic	-0.983	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
V/P	0.9104	likely_pathogenic	0.8243	pathogenic	-0.817	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
V/Q	0.8104	likely_pathogenic	0.7293	pathogenic	-1.157	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
V/R	0.8061	likely_pathogenic	0.7512	pathogenic	-0.677	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
V/S	0.6628	likely_pathogenic	0.5043	ambiguous	-1.43	Destabilizing	0.995	D	0.699	prob.neutral	None	None	None	None	N
V/T	0.5467	ambiguous	0.4289	ambiguous	-1.344	Destabilizing	0.992	D	0.449	neutral	None	None	None	None	N
V/W	0.9415	likely_pathogenic	0.9083	pathogenic	-1.277	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
V/Y	0.822	likely_pathogenic	0.7383	pathogenic	-0.986	Destabilizing	1.0	D	0.807	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.