TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6882	20869;20870;20871	chr2:178725560;178725559;178725558	chr2:179590287;179590286;179590285
N2AB	6565	19918;19919;19920	chr2:178725560;178725559;178725558	chr2:179590287;179590286;179590285
N2A	5638	17137;17138;17139	chr2:178725560;178725559;178725558	chr2:179590287;179590286;179590285
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: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-53
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.4419
• 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
P/L	rs1299399084	-0.138	1.0	D	0.725	0.5	0.8609486	gnomAD-2.1.1	3.18E-05	None	None	None	None	I	None	0	0	None	0	6.45161E-04	None	0	None	0	0	0
P/L	rs1299399084	-0.138	1.0	D	0.725	0.5	0.8609486	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	1.93199E-04	None	0	0	0	0	0
P/L	rs1299399084	-0.138	1.0	D	0.725	0.5	0.8609486	gnomAD-4.0.0	6.57644E-06	None	None	None	None	I	None	0	0	None	0	1.93199E-04	None	0	0	0	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
P/A	0.4213	ambiguous	0.4336	ambiguous	-0.805	Destabilizing	1.0	D	0.661	neutral	N	0.4965421	None	None	I
P/C	0.9343	likely_pathogenic	0.9415	pathogenic	-0.641	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
P/D	0.7574	likely_pathogenic	0.7373	pathogenic	-0.509	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	I
P/E	0.6997	likely_pathogenic	0.6737	pathogenic	-0.584	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	I
P/F	0.9401	likely_pathogenic	0.9421	pathogenic	-0.812	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
P/G	0.7237	likely_pathogenic	0.6945	pathogenic	-0.998	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
P/H	0.6797	likely_pathogenic	0.6886	pathogenic	-0.472	Destabilizing	1.0	D	0.701	prob.neutral	D	0.5230042	None	None	I
P/I	0.8733	likely_pathogenic	0.8656	pathogenic	-0.419	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
P/K	0.7735	likely_pathogenic	0.7798	pathogenic	-0.688	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	I
P/L	0.5923	likely_pathogenic	0.6142	pathogenic	-0.419	Destabilizing	1.0	D	0.725	prob.delet.	D	0.5222437	None	None	I
P/M	0.847	likely_pathogenic	0.8392	pathogenic	-0.451	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
P/N	0.6873	likely_pathogenic	0.6433	pathogenic	-0.413	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	I
P/Q	0.6272	likely_pathogenic	0.6277	pathogenic	-0.626	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	I
P/R	0.6656	likely_pathogenic	0.695	pathogenic	-0.146	Destabilizing	1.0	D	0.738	prob.delet.	D	0.5222437	None	None	I
P/S	0.5446	ambiguous	0.5289	ambiguous	-0.816	Destabilizing	1.0	D	0.699	prob.neutral	N	0.5065061	None	None	I
P/T	0.4935	ambiguous	0.4774	ambiguous	-0.785	Destabilizing	1.0	D	0.681	prob.neutral	N	0.48738784	None	None	I
P/V	0.7429	likely_pathogenic	0.7414	pathogenic	-0.512	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	I
P/W	0.9634	likely_pathogenic	0.9673	pathogenic	-0.909	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	I
P/Y	0.8875	likely_pathogenic	0.8903	pathogenic	-0.626	Destabilizing	1.0	D	0.705	prob.neutral	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.