TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19951	60076;60077;60078	chr2:178592053;178592052;178592051	chr2:179456780;179456779;179456778
N2AB	18310	55153;55154;55155	chr2:178592053;178592052;178592051	chr2:179456780;179456779;179456778
N2A	17383	52372;52373;52374	chr2:178592053;178592052;178592051	chr2:179456780;179456779;179456778
N2B	10886	32881;32882;32883	chr2:178592053;178592052;178592051	chr2:179456780;179456779;179456778
Novex-1	11011	33256;33257;33258	chr2:178592053;178592052;178592051	chr2:179456780;179456779;179456778
Novex-2	11078	33457;33458;33459	chr2:178592053;178592052;178592051	chr2:179456780;179456779;179456778
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: Fn3-32
• Domain position: 75
• Structural Position: 108
• Q(SASA): 0.0734
• 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	rs1576116840	None	0.996	D	0.504	0.403	0.715633265667	gnomAD-4.0.0	3.18576E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72014E-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	0.8893	likely_pathogenic	0.8698	pathogenic	-2.44	Highly Destabilizing	0.994	D	0.576	neutral	D	0.559062807	None	None	N
V/C	0.9821	likely_pathogenic	0.9811	pathogenic	-1.555	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
V/D	0.9993	likely_pathogenic	0.9991	pathogenic	-3.31	Highly Destabilizing	0.269	N	0.731	prob.delet.	None	None	None	None	N
V/E	0.9971	likely_pathogenic	0.9963	pathogenic	-3.003	Highly Destabilizing	0.978	D	0.78	deleterious	D	0.633430465	None	None	N
V/F	0.9595	likely_pathogenic	0.9514	pathogenic	-1.426	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
V/G	0.965	likely_pathogenic	0.9565	pathogenic	-2.989	Highly Destabilizing	0.998	D	0.823	deleterious	D	0.633430465	None	None	N
V/H	0.9994	likely_pathogenic	0.9992	pathogenic	-2.805	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
V/I	0.1201	likely_benign	0.1183	benign	-0.813	Destabilizing	0.996	D	0.504	neutral	D	0.531774252	None	None	N
V/K	0.9978	likely_pathogenic	0.9972	pathogenic	-1.954	Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	N
V/L	0.8214	likely_pathogenic	0.8015	pathogenic	-0.813	Destabilizing	0.996	D	0.572	neutral	N	0.521925563	None	None	N
V/M	0.8876	likely_pathogenic	0.8739	pathogenic	-1.026	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
V/N	0.9978	likely_pathogenic	0.9972	pathogenic	-2.675	Highly Destabilizing	0.998	D	0.886	deleterious	None	None	None	None	N
V/P	0.9982	likely_pathogenic	0.9976	pathogenic	-1.343	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/Q	0.9969	likely_pathogenic	0.9961	pathogenic	-2.314	Highly Destabilizing	0.999	D	0.883	deleterious	None	None	None	None	N
V/R	0.9951	likely_pathogenic	0.9938	pathogenic	-2.078	Highly Destabilizing	0.999	D	0.899	deleterious	None	None	None	None	N
V/S	0.9838	likely_pathogenic	0.981	pathogenic	-3.062	Highly Destabilizing	0.998	D	0.798	deleterious	None	None	None	None	N
V/T	0.9275	likely_pathogenic	0.92	pathogenic	-2.612	Highly Destabilizing	0.996	D	0.595	neutral	None	None	None	None	N
V/W	0.9995	likely_pathogenic	0.9993	pathogenic	-1.867	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
V/Y	0.9971	likely_pathogenic	0.9964	pathogenic	-1.654	Destabilizing	1.0	D	0.775	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.