TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22109	66550;66551;66552	chr2:178582044;178582043;178582042	chr2:179446771;179446770;179446769
N2AB	20468	61627;61628;61629	chr2:178582044;178582043;178582042	chr2:179446771;179446770;179446769
N2A	19541	58846;58847;58848	chr2:178582044;178582043;178582042	chr2:179446771;179446770;179446769
N2B	13044	39355;39356;39357	chr2:178582044;178582043;178582042	chr2:179446771;179446770;179446769
Novex-1	13169	39730;39731;39732	chr2:178582044;178582043;178582042	chr2:179446771;179446770;179446769
Novex-2	13236	39931;39932;39933	chr2:178582044;178582043;178582042	chr2:179446771;179446770;179446769
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: Fn3-48
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.3695
• 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
P/L	rs777960621	-0.235	0.935	N	0.701	0.357	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
P/L	rs777960621	-0.235	0.935	N	0.701	0.357	None	gnomAD-4.0.0	6.15947E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.19755E-06	1.15947E-05	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	0.1568	likely_benign	0.1414	benign	-1.073	Destabilizing	0.025	N	0.303	neutral	N	0.497354168	None	None	N
P/C	0.7649	likely_pathogenic	0.7338	pathogenic	-0.701	Destabilizing	0.997	D	0.771	deleterious	None	None	None	None	N
P/D	0.9132	likely_pathogenic	0.852	pathogenic	-0.72	Destabilizing	0.975	D	0.623	neutral	None	None	None	None	N
P/E	0.7824	likely_pathogenic	0.6711	pathogenic	-0.757	Destabilizing	0.845	D	0.575	neutral	None	None	None	None	N
P/F	0.8535	likely_pathogenic	0.8031	pathogenic	-0.858	Destabilizing	0.997	D	0.759	deleterious	None	None	None	None	N
P/G	0.6799	likely_pathogenic	0.6243	pathogenic	-1.339	Destabilizing	0.845	D	0.607	neutral	None	None	None	None	N
P/H	0.6425	likely_pathogenic	0.5473	ambiguous	-0.839	Destabilizing	0.995	D	0.708	prob.delet.	N	0.503337787	None	None	N
P/I	0.5142	ambiguous	0.4502	ambiguous	-0.469	Destabilizing	0.975	D	0.781	deleterious	None	None	None	None	N
P/K	0.8677	likely_pathogenic	0.7678	pathogenic	-0.919	Destabilizing	0.845	D	0.603	neutral	None	None	None	None	N
P/L	0.2706	likely_benign	0.2209	benign	-0.469	Destabilizing	0.935	D	0.701	prob.neutral	N	0.46758335	None	None	N
P/M	0.4993	ambiguous	0.4352	ambiguous	-0.362	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
P/N	0.6849	likely_pathogenic	0.6072	pathogenic	-0.656	Destabilizing	0.987	D	0.751	deleterious	None	None	None	None	N
P/Q	0.518	ambiguous	0.4354	ambiguous	-0.842	Destabilizing	0.496	N	0.369	neutral	None	None	None	None	N
P/R	0.7689	likely_pathogenic	0.6472	pathogenic	-0.387	Destabilizing	0.967	D	0.758	deleterious	N	0.483949177	None	None	N
P/S	0.3861	ambiguous	0.3337	benign	-1.141	Destabilizing	0.805	D	0.567	neutral	N	0.512880981	None	None	N
P/T	0.2439	likely_benign	0.1972	benign	-1.07	Destabilizing	0.967	D	0.627	neutral	N	0.471154975	None	None	N
P/V	0.3539	ambiguous	0.3031	benign	-0.633	Destabilizing	0.95	D	0.642	neutral	None	None	None	None	N
P/W	0.9291	likely_pathogenic	0.8928	pathogenic	-1.009	Destabilizing	0.999	D	0.744	deleterious	None	None	None	None	N
P/Y	0.7897	likely_pathogenic	0.707	pathogenic	-0.723	Destabilizing	0.996	D	0.771	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.