TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25754	77485;77486;77487	chr2:178568872;178568871;178568870	chr2:179433599;179433598;179433597
N2AB	24113	72562;72563;72564	chr2:178568872;178568871;178568870	chr2:179433599;179433598;179433597
N2A	23186	69781;69782;69783	chr2:178568872;178568871;178568870	chr2:179433599;179433598;179433597
N2B	16689	50290;50291;50292	chr2:178568872;178568871;178568870	chr2:179433599;179433598;179433597
Novex-1	16814	50665;50666;50667	chr2:178568872;178568871;178568870	chr2:179433599;179433598;179433597
Novex-2	16881	50866;50867;50868	chr2:178568872;178568871;178568870	chr2:179433599;179433598;179433597
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-75
• Domain position: 57
• Structural Position: 89
• Q(SASA): 0.2617
• 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
L/P	rs1369560200	-0.739	0.998	N	0.801	0.443	0.801626560535	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	2.87687E-04	0	0
L/P	rs1369560200	-0.739	0.998	N	0.801	0.443	0.801626560535	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
L/P	rs1369560200	-0.739	0.998	N	0.801	0.443	0.801626560535	gnomAD-4.0.0	6.57557E-06	None	None	None	None	N	None	2.41336E-05	0	None	0	0	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
L/A	0.2968	likely_benign	0.3325	benign	-1.558	Destabilizing	0.938	D	0.537	neutral	None	None	None	None	N
L/C	0.441	ambiguous	0.4649	ambiguous	-0.949	Destabilizing	0.334	N	0.388	neutral	None	None	None	None	N
L/D	0.7758	likely_pathogenic	0.8066	pathogenic	-0.868	Destabilizing	0.998	D	0.797	deleterious	None	None	None	None	N
L/E	0.4794	ambiguous	0.5109	ambiguous	-0.725	Destabilizing	0.998	D	0.793	deleterious	None	None	None	None	N
L/F	0.2605	likely_benign	0.2968	benign	-0.821	Destabilizing	0.994	D	0.721	prob.delet.	N	0.472293837	None	None	N
L/G	0.5188	ambiguous	0.5495	ambiguous	-1.997	Destabilizing	0.995	D	0.773	deleterious	None	None	None	None	N
L/H	0.3768	ambiguous	0.4238	ambiguous	-1.172	Destabilizing	0.999	D	0.796	deleterious	N	0.47579933	None	None	N
L/I	0.1974	likely_benign	0.2141	benign	-0.363	Destabilizing	0.958	D	0.443	neutral	N	0.473014626	None	None	N
L/K	0.4037	ambiguous	0.4313	ambiguous	-0.895	Destabilizing	0.995	D	0.749	deleterious	None	None	None	None	N
L/M	0.1258	likely_benign	0.1303	benign	-0.409	Destabilizing	0.998	D	0.716	prob.delet.	None	None	None	None	N
L/N	0.3266	likely_benign	0.3513	ambiguous	-1.071	Destabilizing	0.998	D	0.801	deleterious	None	None	None	None	N
L/P	0.2082	likely_benign	0.2505	benign	-0.734	Destabilizing	0.998	D	0.801	deleterious	N	0.483790225	None	None	N
L/Q	0.1901	likely_benign	0.2085	benign	-1.003	Destabilizing	0.998	D	0.791	deleterious	None	None	None	None	N
L/R	0.3277	likely_benign	0.3547	ambiguous	-0.614	Destabilizing	0.998	D	0.783	deleterious	N	0.507224445	None	None	N
L/S	0.3012	likely_benign	0.3384	benign	-1.805	Destabilizing	0.991	D	0.735	prob.delet.	None	None	None	None	N
L/T	0.1458	likely_benign	0.1558	benign	-1.515	Destabilizing	0.991	D	0.694	prob.neutral	None	None	None	None	N
L/V	0.1394	likely_benign	0.1511	benign	-0.734	Destabilizing	0.958	D	0.473	neutral	N	0.517364081	None	None	N
L/W	0.5225	ambiguous	0.5765	pathogenic	-1.02	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
L/Y	0.5352	ambiguous	0.5808	pathogenic	-0.692	Destabilizing	0.998	D	0.783	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.