TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25255	75988;75989;75990	chr2:178570369;178570368;178570367	chr2:179435096;179435095;179435094
N2AB	23614	71065;71066;71067	chr2:178570369;178570368;178570367	chr2:179435096;179435095;179435094
N2A	22687	68284;68285;68286	chr2:178570369;178570368;178570367	chr2:179435096;179435095;179435094
N2B	16190	48793;48794;48795	chr2:178570369;178570368;178570367	chr2:179435096;179435095;179435094
Novex-1	16315	49168;49169;49170	chr2:178570369;178570368;178570367	chr2:179435096;179435095;179435094
Novex-2	16382	49369;49370;49371	chr2:178570369;178570368;178570367	chr2:179435096;179435095;179435094
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: Fn3-71
• Domain position: 52
• Structural Position: 68
• Q(SASA): 0.2713
• Predicted PPI site: I

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	rs1226764220	-1.462	0.892	N	0.485	0.291	0.589010861393	gnomAD-2.1.1	4.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.97E-06	0
V/A	rs1226764220	-1.462	0.892	N	0.485	0.291	0.589010861393	gnomAD-4.0.0	3.18492E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.71873E-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	0.2048	likely_benign	0.237	benign	-1.335	Destabilizing	0.892	D	0.485	neutral	N	0.475078541	None	None	I
V/C	0.7672	likely_pathogenic	0.8116	pathogenic	-0.946	Destabilizing	0.999	D	0.792	deleterious	None	None	None	None	I
V/D	0.9215	likely_pathogenic	0.9674	pathogenic	-1.086	Destabilizing	0.994	D	0.818	deleterious	D	0.525049666	None	None	I
V/E	0.8414	likely_pathogenic	0.9231	pathogenic	-1.101	Destabilizing	0.987	D	0.784	deleterious	None	None	None	None	I
V/F	0.4019	ambiguous	0.5524	ambiguous	-1.075	Destabilizing	0.935	D	0.723	prob.delet.	N	0.497168814	None	None	I
V/G	0.5543	ambiguous	0.6429	pathogenic	-1.635	Destabilizing	0.983	D	0.781	deleterious	D	0.525303156	None	None	I
V/H	0.9104	likely_pathogenic	0.9585	pathogenic	-1.176	Destabilizing	0.993	D	0.811	deleterious	None	None	None	None	I
V/I	0.1034	likely_benign	0.134	benign	-0.626	Destabilizing	0.773	D	0.496	neutral	N	0.476368761	None	None	I
V/K	0.9111	likely_pathogenic	0.9607	pathogenic	-1.166	Destabilizing	0.987	D	0.795	deleterious	None	None	None	None	I
V/L	0.4336	ambiguous	0.6128	pathogenic	-0.626	Destabilizing	0.63	D	0.497	neutral	N	0.471747178	None	None	I
V/M	0.2484	likely_benign	0.3722	ambiguous	-0.494	Destabilizing	0.996	D	0.701	prob.neutral	None	None	None	None	I
V/N	0.7864	likely_pathogenic	0.8846	pathogenic	-0.962	Destabilizing	0.987	D	0.82	deleterious	None	None	None	None	I
V/P	0.9467	likely_pathogenic	0.969	pathogenic	-0.827	Destabilizing	0.996	D	0.813	deleterious	None	None	None	None	I
V/Q	0.794	likely_pathogenic	0.8869	pathogenic	-1.131	Destabilizing	0.987	D	0.818	deleterious	None	None	None	None	I
V/R	0.8768	likely_pathogenic	0.9356	pathogenic	-0.648	Destabilizing	0.987	D	0.814	deleterious	None	None	None	None	I
V/S	0.4398	ambiguous	0.523	ambiguous	-1.462	Destabilizing	0.987	D	0.782	deleterious	None	None	None	None	I
V/T	0.2477	likely_benign	0.3068	benign	-1.364	Destabilizing	0.957	D	0.545	neutral	None	None	None	None	I
V/W	0.9565	likely_pathogenic	0.9804	pathogenic	-1.251	Destabilizing	0.997	D	0.793	deleterious	None	None	None	None	I
V/Y	0.8652	likely_pathogenic	0.9287	pathogenic	-0.953	Destabilizing	0.073	N	0.302	neutral	None	None	None	None	I

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.