TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23744	71455;71456;71457	chr2:178574902;178574901;178574900	chr2:179439629;179439628;179439627
N2AB	22103	66532;66533;66534	chr2:178574902;178574901;178574900	chr2:179439629;179439628;179439627
N2A	21176	63751;63752;63753	chr2:178574902;178574901;178574900	chr2:179439629;179439628;179439627
N2B	14679	44260;44261;44262	chr2:178574902;178574901;178574900	chr2:179439629;179439628;179439627
Novex-1	14804	44635;44636;44637	chr2:178574902;178574901;178574900	chr2:179439629;179439628;179439627
Novex-2	14871	44836;44837;44838	chr2:178574902;178574901;178574900	chr2:179439629;179439628;179439627
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: 19
• Structural Position: 20
• Q(SASA): 0.046
• 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	rs2154171872	None	0.008	N	0.222	0.058	0.322230723748	gnomAD-4.0.0	3.18712E-06	None	None	None	None	N	None	0	0	None	0	2.79049E-05	None	0	0	2.86115E-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	0.4655	ambiguous	0.4086	ambiguous	-1.869	Destabilizing	0.722	D	0.653	neutral	N	0.499242467	None	None	N
V/C	0.7684	likely_pathogenic	0.7384	pathogenic	-0.771	Destabilizing	0.996	D	0.788	deleterious	None	None	None	None	N
V/D	0.9923	likely_pathogenic	0.9894	pathogenic	-2.608	Highly Destabilizing	0.987	D	0.86	deleterious	None	None	None	None	N
V/E	0.9804	likely_pathogenic	0.9735	pathogenic	-2.275	Highly Destabilizing	0.949	D	0.85	deleterious	D	0.522054834	None	None	N
V/F	0.5666	likely_pathogenic	0.5123	ambiguous	-0.988	Destabilizing	0.923	D	0.85	deleterious	None	None	None	None	N
V/G	0.808	likely_pathogenic	0.7709	pathogenic	-2.465	Highly Destabilizing	0.949	D	0.856	deleterious	N	0.503950579	None	None	N
V/H	0.9888	likely_pathogenic	0.9838	pathogenic	-2.539	Highly Destabilizing	0.996	D	0.823	deleterious	None	None	None	None	N
V/I	0.0782	likely_benign	0.0716	benign	-0.11	Destabilizing	0.008	N	0.222	neutral	N	0.45029094	None	None	N
V/K	0.9837	likely_pathogenic	0.9775	pathogenic	-1.16	Destabilizing	0.923	D	0.843	deleterious	None	None	None	None	N
V/L	0.2145	likely_benign	0.1684	benign	-0.11	Destabilizing	0.008	N	0.334	neutral	N	0.454179394	None	None	N
V/M	0.2554	likely_benign	0.2116	benign	-0.377	Destabilizing	0.415	N	0.502	neutral	None	None	None	None	N
V/N	0.9696	likely_pathogenic	0.9556	pathogenic	-1.967	Destabilizing	0.961	D	0.856	deleterious	None	None	None	None	N
V/P	0.9924	likely_pathogenic	0.9899	pathogenic	-0.683	Destabilizing	0.987	D	0.829	deleterious	None	None	None	None	N
V/Q	0.964	likely_pathogenic	0.9523	pathogenic	-1.481	Destabilizing	0.961	D	0.827	deleterious	None	None	None	None	N
V/R	0.9703	likely_pathogenic	0.9625	pathogenic	-1.664	Destabilizing	0.961	D	0.853	deleterious	None	None	None	None	N
V/S	0.8232	likely_pathogenic	0.7826	pathogenic	-2.303	Highly Destabilizing	0.923	D	0.823	deleterious	None	None	None	None	N
V/T	0.677	likely_pathogenic	0.6234	pathogenic	-1.801	Destabilizing	0.775	D	0.72	prob.delet.	None	None	None	None	N
V/W	0.9918	likely_pathogenic	0.9871	pathogenic	-1.392	Destabilizing	0.996	D	0.809	deleterious	None	None	None	None	N
V/Y	0.9522	likely_pathogenic	0.9375	pathogenic	-1.149	Destabilizing	0.961	D	0.834	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.