TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8954	27085;27086;27087	chr2:178713274;178713273;178713272	chr2:179578001;179578000;179577999
N2AB	8637	26134;26135;26136	chr2:178713274;178713273;178713272	chr2:179578001;179578000;179577999
N2A	7710	23353;23354;23355	chr2:178713274;178713273;178713272	chr2:179578001;179578000;179577999
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: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-75
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.6853
• 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	rs752903252	0.046	0.999	N	0.667	0.403	0.724535380459	gnomAD-2.1.1	4.12E-06	None	None	None	None	I	None	0	0	None	0	5.72E-05	None	0	None	0	0	0
P/L	rs752903252	0.046	0.999	N	0.667	0.403	0.724535380459	gnomAD-4.0.0	2.74301E-06	None	None	None	None	I	None	0	0	None	0	7.58112E-05	None	0	0	9.00807E-07	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	0.2483	likely_benign	0.3498	ambiguous	-0.37	Destabilizing	0.992	D	0.629	neutral	N	0.472971091	None	None	I
P/C	0.8573	likely_pathogenic	0.9177	pathogenic	-0.675	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
P/D	0.7492	likely_pathogenic	0.8271	pathogenic	-0.29	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	I
P/E	0.609	likely_pathogenic	0.7175	pathogenic	-0.412	Destabilizing	0.998	D	0.613	neutral	None	None	None	None	I
P/F	0.8166	likely_pathogenic	0.8947	pathogenic	-0.695	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	I
P/G	0.6573	likely_pathogenic	0.7629	pathogenic	-0.461	Destabilizing	0.999	D	0.619	neutral	None	None	None	None	I
P/H	0.5513	ambiguous	0.6764	pathogenic	-0.075	Destabilizing	1.0	D	0.65	neutral	None	None	None	None	I
P/I	0.6513	likely_pathogenic	0.7744	pathogenic	-0.283	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
P/K	0.6689	likely_pathogenic	0.7896	pathogenic	-0.395	Destabilizing	0.833	D	0.433	neutral	None	None	None	None	I
P/L	0.3511	ambiguous	0.4839	ambiguous	-0.283	Destabilizing	0.999	D	0.667	neutral	N	0.507065022	None	None	I
P/M	0.634	likely_pathogenic	0.7525	pathogenic	-0.431	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	I
P/N	0.6868	likely_pathogenic	0.7861	pathogenic	-0.157	Destabilizing	0.999	D	0.656	neutral	None	None	None	None	I
P/Q	0.4526	ambiguous	0.5841	pathogenic	-0.391	Destabilizing	0.998	D	0.627	neutral	N	0.49321029	None	None	I
P/R	0.4749	ambiguous	0.6259	pathogenic	0.09	Stabilizing	0.995	D	0.663	neutral	N	0.489017978	None	None	I
P/S	0.3891	ambiguous	0.5224	ambiguous	-0.475	Destabilizing	0.998	D	0.618	neutral	N	0.46829599	None	None	I
P/T	0.3349	likely_benign	0.4541	ambiguous	-0.501	Destabilizing	0.999	D	0.631	neutral	N	0.436626288	None	None	I
P/V	0.4836	ambiguous	0.619	pathogenic	-0.28	Destabilizing	0.999	D	0.662	neutral	None	None	None	None	I
P/W	0.9189	likely_pathogenic	0.9559	pathogenic	-0.769	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
P/Y	0.7942	likely_pathogenic	0.876	pathogenic	-0.476	Destabilizing	1.0	D	0.677	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.