TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3478	10657;10658;10659	chr2:178757788;178757787;178757786	chr2:179622515;179622514;179622513
N2AB	None	None	chr2:None	chr2:None
N2A	None	None	chr2:None	chr2:None
N2B	None	None	chr2:None	chr2:None
Novex-1	3432	10519;10520;10521	chr2:178757788;178757787;178757786	chr2:179622515;179622514;179622513
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-25
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.352
• Predicted PPI site: I

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
N/D	rs771324532	-0.024	None	None	None	0.078	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
N/D	rs771324532	-0.024	None	None	None	0.078	None	gnomAD-4.0.0	1.59162E-06	None	None	None	None	I	None	0	2.28645E-05	None	0	0	None	0	0	0	0	0
N/K	None	None	None	None	None	0.102	None	gnomAD-4.0.0	1.36854E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99544E-07	1.1598E-05	0
N/S	None	None	None	None	None	0.117	None	gnomAD-4.0.0	1.20034E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31252E-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
N/A	0.1199	likely_benign	None	None	-0.747	Destabilizing	None	None	None	None	None	None	None	None	I
N/C	0.1199	likely_benign	None	None	0.173	Stabilizing	None	None	None	None	None	None	None	None	I
N/D	0.1213	likely_benign	None	None	0.017	Stabilizing	None	None	None	None	None	None	None	None	I
N/E	0.2533	likely_benign	None	None	0.059	Stabilizing	None	None	None	None	None	None	None	None	I
N/F	0.4665	ambiguous	None	None	-0.663	Destabilizing	None	None	None	None	None	None	None	None	I
N/G	0.1688	likely_benign	None	None	-1.032	Destabilizing	None	None	None	None	None	None	None	None	I
N/H	0.1007	likely_benign	None	None	-0.819	Destabilizing	None	None	None	None	None	None	None	None	I
N/I	0.1461	likely_benign	None	None	-0.048	Destabilizing	None	None	None	None	None	None	None	None	I
N/K	0.2485	likely_benign	None	None	-0.191	Destabilizing	None	None	None	None	None	None	None	None	I
N/L	0.169	likely_benign	None	None	-0.048	Destabilizing	None	None	None	None	None	None	None	None	I
N/M	0.2668	likely_benign	None	None	0.318	Stabilizing	None	None	None	None	None	None	None	None	I
N/P	0.3252	likely_benign	None	None	-0.252	Destabilizing	None	None	None	None	None	None	None	None	I
N/Q	0.2536	likely_benign	None	None	-0.609	Destabilizing	None	None	None	None	None	None	None	None	I
N/R	0.2196	likely_benign	None	None	-0.181	Destabilizing	None	None	None	None	None	None	None	None	I
N/S	0.0459	likely_benign	None	None	-0.603	Destabilizing	None	None	None	None	None	None	None	None	I
N/T	0.0834	likely_benign	None	None	-0.382	Destabilizing	None	None	None	None	None	None	None	None	I
N/V	0.1665	likely_benign	None	None	-0.252	Destabilizing	None	None	None	None	None	None	None	None	I
N/W	0.6163	likely_pathogenic	None	None	-0.481	Destabilizing	None	None	None	None	None	None	None	None	I
N/Y	0.1405	likely_benign	None	None	-0.297	Destabilizing	None	None	None	None	None	None	None	None	I

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.