TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14011	42256;42257;42258	chr2:178634843;178634842;178634841	chr2:179499570;179499569;179499568
N2AB	12370	37333;37334;37335	chr2:178634843;178634842;178634841	chr2:179499570;179499569;179499568
N2A	11443	34552;34553;34554	chr2:178634843;178634842;178634841	chr2:179499570;179499569;179499568
N2B	4946	15061;15062;15063	chr2:178634843;178634842;178634841	chr2:179499570;179499569;179499568
Novex-1	5071	15436;15437;15438	chr2:178634843;178634842;178634841	chr2:179499570;179499569;179499568
Novex-2	5138	15637;15638;15639	chr2:178634843;178634842;178634841	chr2:179499570;179499569;179499568
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-90
• Domain position: 47
• Structural Position: 122
• Q(SASA): 0.2903
• 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
E/K	None	None	0.115	N	0.478	0.159	0.151104730317	gnomAD-4.0.0	1.60873E-06	None	None	None	None	N	None	0	0	None	0	2.78474E-05	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
E/A	0.7115	likely_pathogenic	0.5702	pathogenic	-0.73	Destabilizing	0.115	N	0.495	neutral	N	0.470307632	None	None	N
E/C	0.9916	likely_pathogenic	0.9851	pathogenic	-0.315	Destabilizing	0.934	D	0.807	deleterious	None	None	None	None	N
E/D	0.2918	likely_benign	0.2839	benign	-1.04	Destabilizing	None	N	0.153	neutral	N	0.431336527	None	None	N
E/F	0.9826	likely_pathogenic	0.9623	pathogenic	-0.524	Destabilizing	0.789	D	0.787	deleterious	None	None	None	None	N
E/G	0.8699	likely_pathogenic	0.7262	pathogenic	-1.052	Destabilizing	0.115	N	0.608	neutral	N	0.472079038	None	None	N
E/H	0.9355	likely_pathogenic	0.867	pathogenic	-0.892	Destabilizing	0.552	D	0.484	neutral	None	None	None	None	N
E/I	0.8484	likely_pathogenic	0.7521	pathogenic	0.131	Stabilizing	0.552	D	0.774	deleterious	None	None	None	None	N
E/K	0.7957	likely_pathogenic	0.5953	pathogenic	-0.56	Destabilizing	0.115	N	0.478	neutral	N	0.431668438	None	None	N
E/L	0.9227	likely_pathogenic	0.8387	pathogenic	0.131	Stabilizing	0.378	N	0.761	deleterious	None	None	None	None	N
E/M	0.9148	likely_pathogenic	0.8411	pathogenic	0.596	Stabilizing	0.934	D	0.734	deleterious	None	None	None	None	N
E/N	0.7594	likely_pathogenic	0.6302	pathogenic	-0.86	Destabilizing	0.08	N	0.474	neutral	None	None	None	None	N
E/P	0.9986	likely_pathogenic	0.9967	pathogenic	-0.134	Destabilizing	0.552	D	0.499	neutral	None	None	None	None	N
E/Q	0.5713	likely_pathogenic	0.4026	ambiguous	-0.76	Destabilizing	0.115	N	0.519	neutral	N	0.435316161	None	None	N
E/R	0.897	likely_pathogenic	0.7759	pathogenic	-0.41	Destabilizing	0.378	N	0.466	neutral	None	None	None	None	N
E/S	0.7322	likely_pathogenic	0.5904	pathogenic	-1.14	Destabilizing	0.08	N	0.449	neutral	None	None	None	None	N
E/T	0.7569	likely_pathogenic	0.607	pathogenic	-0.883	Destabilizing	0.147	N	0.519	neutral	None	None	None	None	N
E/V	0.6903	likely_pathogenic	0.5602	ambiguous	-0.134	Destabilizing	0.481	N	0.634	neutral	N	0.414820728	None	None	N
E/W	0.9967	likely_pathogenic	0.9924	pathogenic	-0.397	Destabilizing	0.934	D	0.749	deleterious	None	None	None	None	N
E/Y	0.9761	likely_pathogenic	0.9487	pathogenic	-0.313	Destabilizing	0.789	D	0.742	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.