TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23763	71512;71513;71514	chr2:178574845;178574844;178574843	chr2:179439572;179439571;179439570
N2AB	22122	66589;66590;66591	chr2:178574845;178574844;178574843	chr2:179439572;179439571;179439570
N2A	21195	63808;63809;63810	chr2:178574845;178574844;178574843	chr2:179439572;179439571;179439570
N2B	14698	44317;44318;44319	chr2:178574845;178574844;178574843	chr2:179439572;179439571;179439570
Novex-1	14823	44692;44693;44694	chr2:178574845;178574844;178574843	chr2:179439572;179439571;179439570
Novex-2	14890	44893;44894;44895	chr2:178574845;178574844;178574843	chr2:179439572;179439571;179439570
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: Fn3-60
• Domain position: 38
• Structural Position: 39
• Q(SASA): 0.1541
• 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/I	None	None	None	N	0.225	0.065	0.350524144436	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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	0.3816	ambiguous	0.3388	benign	-2.489	Highly Destabilizing	0.104	N	0.618	neutral	N	0.468290911	None	None	I
V/C	0.7578	likely_pathogenic	0.7524	pathogenic	-2.289	Highly Destabilizing	0.968	D	0.709	prob.delet.	None	None	None	None	I
V/D	0.8106	likely_pathogenic	0.7743	pathogenic	-3.512	Highly Destabilizing	0.726	D	0.793	deleterious	None	None	None	None	I
V/E	0.6161	likely_pathogenic	0.5673	pathogenic	-3.348	Highly Destabilizing	0.667	D	0.728	prob.delet.	N	0.508587095	None	None	I
V/F	0.3589	ambiguous	0.2909	benign	-1.476	Destabilizing	0.567	D	0.723	prob.delet.	None	None	None	None	I
V/G	0.5971	likely_pathogenic	0.5557	ambiguous	-2.928	Highly Destabilizing	0.667	D	0.765	deleterious	N	0.493587643	None	None	I
V/H	0.7361	likely_pathogenic	0.6928	pathogenic	-2.393	Highly Destabilizing	0.968	D	0.777	deleterious	None	None	None	None	I
V/I	0.0694	likely_benign	0.067	benign	-1.266	Destabilizing	None	N	0.225	neutral	N	0.422453765	None	None	I
V/K	0.6078	likely_pathogenic	0.5542	ambiguous	-2.176	Highly Destabilizing	0.726	D	0.729	prob.delet.	None	None	None	None	I
V/L	0.2634	likely_benign	0.2587	benign	-1.266	Destabilizing	0.009	N	0.436	neutral	N	0.505800293	None	None	I
V/M	0.1824	likely_benign	0.1664	benign	-1.466	Destabilizing	0.567	D	0.689	prob.neutral	None	None	None	None	I
V/N	0.5754	likely_pathogenic	0.5175	ambiguous	-2.488	Highly Destabilizing	0.89	D	0.807	deleterious	None	None	None	None	I
V/P	0.9901	likely_pathogenic	0.9903	pathogenic	-1.651	Destabilizing	0.89	D	0.725	prob.delet.	None	None	None	None	I
V/Q	0.5524	ambiguous	0.5022	ambiguous	-2.441	Highly Destabilizing	0.89	D	0.735	prob.delet.	None	None	None	None	I
V/R	0.5377	ambiguous	0.4784	ambiguous	-1.757	Destabilizing	0.726	D	0.807	deleterious	None	None	None	None	I
V/S	0.4319	ambiguous	0.3798	ambiguous	-2.982	Highly Destabilizing	0.726	D	0.7	prob.neutral	None	None	None	None	I
V/T	0.238	likely_benign	0.2072	benign	-2.707	Highly Destabilizing	0.272	N	0.649	neutral	None	None	None	None	I
V/W	0.9169	likely_pathogenic	0.8901	pathogenic	-1.914	Destabilizing	0.968	D	0.743	deleterious	None	None	None	None	I
V/Y	0.7653	likely_pathogenic	0.7061	pathogenic	-1.68	Destabilizing	0.726	D	0.727	prob.delet.	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.