TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10125	30598;30599;30600	chr2:178702514;178702513;178702512	chr2:179567241;179567240;179567239
N2AB	9808	29647;29648;29649	chr2:178702514;178702513;178702512	chr2:179567241;179567240;179567239
N2A	8881	26866;26867;26868	chr2:178702514;178702513;178702512	chr2:179567241;179567240;179567239
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-86
• Domain position: 48
• Structural Position: 123
• Q(SASA): 0.2118
• 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
F/I	None	None	0.978	None	0.531	0.428	0.405979908929	gnomAD-4.0.0	1.59085E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85744E-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
F/A	0.9976	likely_pathogenic	0.998	pathogenic	-2.404	Highly Destabilizing	0.996	D	0.647	neutral	None	None	None	None	N
F/C	0.9918	likely_pathogenic	0.9925	pathogenic	-1.262	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
F/D	0.9992	likely_pathogenic	0.9995	pathogenic	-1.562	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
F/E	0.999	likely_pathogenic	0.9993	pathogenic	-1.454	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
F/G	0.999	likely_pathogenic	0.9991	pathogenic	-2.772	Highly Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
F/H	0.992	likely_pathogenic	0.9939	pathogenic	-1.105	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
F/I	0.925	likely_pathogenic	0.9253	pathogenic	-1.267	Destabilizing	0.978	D	0.531	neutral	None	None	None	None	N
F/K	0.9981	likely_pathogenic	0.9984	pathogenic	-1.326	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
F/L	0.9961	likely_pathogenic	0.9963	pathogenic	-1.267	Destabilizing	0.217	N	0.26	neutral	None	None	None	None	N
F/M	0.9758	likely_pathogenic	0.9803	pathogenic	-0.886	Destabilizing	0.998	D	0.645	neutral	None	None	None	None	N
F/N	0.9974	likely_pathogenic	0.9982	pathogenic	-1.429	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
F/P	0.9999	likely_pathogenic	0.9999	pathogenic	-1.644	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
F/Q	0.9973	likely_pathogenic	0.9979	pathogenic	-1.514	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
F/R	0.9949	likely_pathogenic	0.9953	pathogenic	-0.676	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
F/S	0.9972	likely_pathogenic	0.998	pathogenic	-2.216	Highly Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
F/T	0.9956	likely_pathogenic	0.9969	pathogenic	-2.005	Highly Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
F/V	0.9571	likely_pathogenic	0.9605	pathogenic	-1.644	Destabilizing	0.978	D	0.581	neutral	None	None	None	None	N
F/W	0.9542	likely_pathogenic	0.9624	pathogenic	-0.576	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	N
F/Y	0.7566	likely_pathogenic	0.7914	pathogenic	-0.788	Destabilizing	0.998	D	0.555	neutral	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.