TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24160	72703;72704;72705	chr2:178573654;178573653;178573652	chr2:179438381;179438380;179438379
N2AB	22519	67780;67781;67782	chr2:178573654;178573653;178573652	chr2:179438381;179438380;179438379
N2A	21592	64999;65000;65001	chr2:178573654;178573653;178573652	chr2:179438381;179438380;179438379
N2B	15095	45508;45509;45510	chr2:178573654;178573653;178573652	chr2:179438381;179438380;179438379
Novex-1	15220	45883;45884;45885	chr2:178573654;178573653;178573652	chr2:179438381;179438380;179438379
Novex-2	15287	46084;46085;46086	chr2:178573654;178573653;178573652	chr2:179438381;179438380;179438379
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: Fn3-63
• Domain position: 39
• Structural Position: 40
• Q(SASA): 0.1086
• 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/L	None	None	0.009	N	0.352	0.24	0.358540694251	gnomAD-4.0.0	1.88852E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.29086E-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	0.821	likely_pathogenic	0.8671	pathogenic	-2.419	Highly Destabilizing	0.104	N	0.575	neutral	D	0.534400142	None	None	N
V/C	0.9315	likely_pathogenic	0.9441	pathogenic	-2.16	Highly Destabilizing	0.968	D	0.773	deleterious	None	None	None	None	N
V/D	0.9984	likely_pathogenic	0.9986	pathogenic	-3.414	Highly Destabilizing	0.726	D	0.895	deleterious	None	None	None	None	N
V/E	0.9937	likely_pathogenic	0.9947	pathogenic	-3.101	Highly Destabilizing	0.667	D	0.864	deleterious	D	0.558037805	None	None	N
V/F	0.8093	likely_pathogenic	0.8507	pathogenic	-1.37	Destabilizing	0.567	D	0.757	deleterious	None	None	None	None	N
V/G	0.9467	likely_pathogenic	0.9577	pathogenic	-3.053	Highly Destabilizing	0.667	D	0.881	deleterious	D	0.558037805	None	None	N
V/H	0.9971	likely_pathogenic	0.9978	pathogenic	-2.898	Highly Destabilizing	0.968	D	0.882	deleterious	None	None	None	None	N
V/I	0.0639	likely_benign	0.067	benign	-0.59	Destabilizing	None	N	0.183	neutral	N	0.438639512	None	None	N
V/K	0.9954	likely_pathogenic	0.9961	pathogenic	-2.103	Highly Destabilizing	0.726	D	0.863	deleterious	None	None	None	None	N
V/L	0.3206	likely_benign	0.3914	ambiguous	-0.59	Destabilizing	0.009	N	0.352	neutral	N	0.4972106	None	None	N
V/M	0.5884	likely_pathogenic	0.6699	pathogenic	-0.889	Destabilizing	0.567	D	0.643	neutral	None	None	None	None	N
V/N	0.9936	likely_pathogenic	0.995	pathogenic	-2.744	Highly Destabilizing	0.89	D	0.907	deleterious	None	None	None	None	N
V/P	0.9909	likely_pathogenic	0.9917	pathogenic	-1.178	Destabilizing	0.89	D	0.868	deleterious	None	None	None	None	N
V/Q	0.9912	likely_pathogenic	0.9932	pathogenic	-2.416	Highly Destabilizing	0.89	D	0.889	deleterious	None	None	None	None	N
V/R	0.9905	likely_pathogenic	0.992	pathogenic	-2.112	Highly Destabilizing	0.726	D	0.902	deleterious	None	None	None	None	N
V/S	0.9666	likely_pathogenic	0.9756	pathogenic	-3.339	Highly Destabilizing	0.726	D	0.81	deleterious	None	None	None	None	N
V/T	0.8876	likely_pathogenic	0.9142	pathogenic	-2.857	Highly Destabilizing	0.272	N	0.591	neutral	None	None	None	None	N
V/W	0.996	likely_pathogenic	0.997	pathogenic	-1.963	Destabilizing	0.968	D	0.861	deleterious	None	None	None	None	N
V/Y	0.9852	likely_pathogenic	0.9888	pathogenic	-1.614	Destabilizing	0.726	D	0.761	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.