TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14482	43669;43670;43671	chr2:178632562;178632561;178632560	chr2:179497289;179497288;179497287
N2AB	12841	38746;38747;38748	chr2:178632562;178632561;178632560	chr2:179497289;179497288;179497287
N2A	11914	35965;35966;35967	chr2:178632562;178632561;178632560	chr2:179497289;179497288;179497287
N2B	5417	16474;16475;16476	chr2:178632562;178632561;178632560	chr2:179497289;179497288;179497287
Novex-1	5542	16849;16850;16851	chr2:178632562;178632561;178632560	chr2:179497289;179497288;179497287
Novex-2	5609	17050;17051;17052	chr2:178632562;178632561;178632560	chr2:179497289;179497288;179497287
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-95
• Domain position: 75
• Structural Position: 159
• Q(SASA): 0.3969
• 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	0.999	N	0.663	0.418	0.549796516352	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	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	0.4988	ambiguous	0.5256	ambiguous	-0.734	Destabilizing	0.999	D	0.679	prob.neutral	N	0.501827228	None	None	N
E/C	0.9817	likely_pathogenic	0.9826	pathogenic	-0.381	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
E/D	0.5986	likely_pathogenic	0.5798	pathogenic	-1.083	Destabilizing	0.999	D	0.497	neutral	N	0.507562541	None	None	N
E/F	0.9844	likely_pathogenic	0.9841	pathogenic	-0.38	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
E/G	0.2868	likely_benign	0.2802	benign	-1.072	Destabilizing	1.0	D	0.729	prob.delet.	N	0.506258393	None	None	N
E/H	0.9555	likely_pathogenic	0.9534	pathogenic	-0.701	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
E/I	0.9531	likely_pathogenic	0.9487	pathogenic	0.175	Stabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/K	0.5627	ambiguous	0.5461	ambiguous	-0.62	Destabilizing	0.999	D	0.663	neutral	N	0.50277546	None	None	N
E/L	0.9113	likely_pathogenic	0.91	pathogenic	0.175	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/M	0.9088	likely_pathogenic	0.9089	pathogenic	0.567	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/N	0.8144	likely_pathogenic	0.7955	pathogenic	-0.962	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/P	0.9798	likely_pathogenic	0.9797	pathogenic	-0.107	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
E/Q	0.4884	ambiguous	0.4793	ambiguous	-0.844	Destabilizing	1.0	D	0.669	neutral	N	0.506554908	None	None	N
E/R	0.7165	likely_pathogenic	0.7096	pathogenic	-0.395	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
E/S	0.6564	likely_pathogenic	0.6582	pathogenic	-1.238	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
E/T	0.8379	likely_pathogenic	0.8393	pathogenic	-0.97	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/V	0.84	likely_pathogenic	0.8419	pathogenic	-0.107	Destabilizing	1.0	D	0.775	deleterious	N	0.511925286	None	None	N
E/W	0.9961	likely_pathogenic	0.9962	pathogenic	-0.217	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/Y	0.977	likely_pathogenic	0.977	pathogenic	-0.163	Destabilizing	1.0	D	0.757	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.