TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19183	57772;57773;57774	chr2:178595807;178595806;178595805	chr2:179460534;179460533;179460532
N2AB	17542	52849;52850;52851	chr2:178595807;178595806;178595805	chr2:179460534;179460533;179460532
N2A	16615	50068;50069;50070	chr2:178595807;178595806;178595805	chr2:179460534;179460533;179460532
N2B	10118	30577;30578;30579	chr2:178595807;178595806;178595805	chr2:179460534;179460533;179460532
Novex-1	10243	30952;30953;30954	chr2:178595807;178595806;178595805	chr2:179460534;179460533;179460532
Novex-2	10310	31153;31154;31155	chr2:178595807;178595806;178595805	chr2:179460534;179460533;179460532
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: Fn3-27
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.4186
• 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	None	None	0.997	N	0.463	0.25	0.53099781502	gnomAD-4.0.0	6.94541E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.0801E-07	0	0
V/I	None	None	0.994	N	0.523	0.264	0.451023696535	gnomAD-4.0.0	1.64899E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.53036E-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	0.3796	ambiguous	0.4122	ambiguous	-0.705	Destabilizing	0.997	D	0.463	neutral	N	0.451840546	None	None	I
V/C	0.8057	likely_pathogenic	0.8274	pathogenic	-0.75	Destabilizing	1.0	D	0.699	prob.delet.	None	None	None	None	I
V/D	0.8639	likely_pathogenic	0.8821	pathogenic	-0.246	Destabilizing	0.999	D	0.806	deleterious	N	0.488697847	None	None	I
V/E	0.642	likely_pathogenic	0.6981	pathogenic	-0.351	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	I
V/F	0.4802	ambiguous	0.5191	ambiguous	-0.953	Destabilizing	0.999	D	0.691	prob.delet.	N	0.477088052	None	None	I
V/G	0.6164	likely_pathogenic	0.654	pathogenic	-0.844	Destabilizing	0.999	D	0.755	deleterious	N	0.488444357	None	None	I
V/H	0.8347	likely_pathogenic	0.8607	pathogenic	-0.373	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
V/I	0.0879	likely_benign	0.0901	benign	-0.483	Destabilizing	0.994	D	0.523	neutral	N	0.510618962	None	None	I
V/K	0.491	ambiguous	0.5503	ambiguous	-0.347	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	I
V/L	0.4829	ambiguous	0.4992	ambiguous	-0.483	Destabilizing	0.994	D	0.514	neutral	N	0.45398014	None	None	I
V/M	0.2775	likely_benign	0.3165	benign	-0.362	Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	I
V/N	0.6396	likely_pathogenic	0.6753	pathogenic	-0.135	Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	I
V/P	0.8535	likely_pathogenic	0.8438	pathogenic	-0.522	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	I
V/Q	0.5428	ambiguous	0.5793	pathogenic	-0.424	Destabilizing	0.999	D	0.848	deleterious	None	None	None	None	I
V/R	0.4464	ambiguous	0.483	ambiguous	0.157	Stabilizing	0.999	D	0.831	deleterious	None	None	None	None	I
V/S	0.4571	ambiguous	0.5002	ambiguous	-0.584	Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	I
V/T	0.2649	likely_benign	0.2959	benign	-0.589	Destabilizing	0.998	D	0.697	prob.delet.	None	None	None	None	I
V/W	0.9663	likely_pathogenic	0.9724	pathogenic	-0.971	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
V/Y	0.8518	likely_pathogenic	0.8716	pathogenic	-0.652	Destabilizing	0.999	D	0.728	deleterious	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.