TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3384	10375;10376;10377	chr2:178759137;178759136;178759135	chr2:179623864;179623863;179623862
N2AB	3384	10375;10376;10377	chr2:178759137;178759136;178759135	chr2:179623864;179623863;179623862
N2A	3384	10375;10376;10377	chr2:178759137;178759136;178759135	chr2:179623864;179623863;179623862
N2B	3338	10237;10238;10239	chr2:178759137;178759136;178759135	chr2:179623864;179623863;179623862
Novex-1	3338	10237;10238;10239	chr2:178759137;178759136;178759135	chr2:179623864;179623863;179623862
Novex-2	3338	10237;10238;10239	chr2:178759137;178759136;178759135	chr2:179623864;179623863;179623862
Novex-3	3384	10375;10376;10377	chr2:178759137;178759136;178759135	chr2:179623864;179623863;179623862

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-24
• Domain position: 40
• Structural Position: 58
• Q(SASA): 0.1591
• 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
I/M	None	None	1.0	D	0.732	0.498	0.386234084001	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
I/S	None	None	1.0	D	0.749	0.716	0.899799008202	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
I/A	0.9425	likely_pathogenic	0.9569	pathogenic	-2.104	Highly Destabilizing	0.999	D	0.517	neutral	None	None	None	None	N
I/C	0.9776	likely_pathogenic	0.9821	pathogenic	-1.157	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
I/D	0.9952	likely_pathogenic	0.9964	pathogenic	-2.616	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
I/E	0.9775	likely_pathogenic	0.9831	pathogenic	-2.357	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
I/F	0.6273	likely_pathogenic	0.7057	pathogenic	-1.334	Destabilizing	1.0	D	0.69	prob.neutral	D	0.645036204	None	None	N
I/G	0.9851	likely_pathogenic	0.9869	pathogenic	-2.634	Highly Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
I/H	0.9803	likely_pathogenic	0.9862	pathogenic	-2.223	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
I/K	0.9586	likely_pathogenic	0.9685	pathogenic	-1.538	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
I/L	0.2213	likely_benign	0.2752	benign	-0.559	Destabilizing	0.993	D	0.421	neutral	N	0.488852044	None	None	N
I/M	0.2199	likely_benign	0.2458	benign	-0.439	Destabilizing	1.0	D	0.732	prob.delet.	D	0.579719839	None	None	N
I/N	0.9316	likely_pathogenic	0.9454	pathogenic	-2.011	Highly Destabilizing	1.0	D	0.855	deleterious	D	0.662598185	None	None	N
I/P	0.9873	likely_pathogenic	0.9871	pathogenic	-1.058	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
I/Q	0.9559	likely_pathogenic	0.969	pathogenic	-1.802	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
I/R	0.9372	likely_pathogenic	0.9519	pathogenic	-1.477	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
I/S	0.9586	likely_pathogenic	0.9671	pathogenic	-2.606	Highly Destabilizing	1.0	D	0.749	deleterious	D	0.661719911	None	None	N
I/T	0.9443	likely_pathogenic	0.964	pathogenic	-2.196	Highly Destabilizing	1.0	D	0.695	prob.neutral	D	0.656463123	None	None	N
I/V	0.2319	likely_benign	0.2838	benign	-1.058	Destabilizing	0.993	D	0.411	neutral	N	0.507049618	None	None	N
I/W	0.9781	likely_pathogenic	0.9805	pathogenic	-1.764	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
I/Y	0.9304	likely_pathogenic	0.9423	pathogenic	-1.379	Destabilizing	1.0	D	0.769	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.