TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19646	59161;59162;59163	chr2:178593272;178593271;178593270	chr2:179457999;179457998;179457997
N2AB	18005	54238;54239;54240	chr2:178593272;178593271;178593270	chr2:179457999;179457998;179457997
N2A	17078	51457;51458;51459	chr2:178593272;178593271;178593270	chr2:179457999;179457998;179457997
N2B	10581	31966;31967;31968	chr2:178593272;178593271;178593270	chr2:179457999;179457998;179457997
Novex-1	10706	32341;32342;32343	chr2:178593272;178593271;178593270	chr2:179457999;179457998;179457997
Novex-2	10773	32542;32543;32544	chr2:178593272;178593271;178593270	chr2:179457999;179457998;179457997
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: Fn3-30
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.5728
• 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/Q	None	None	0.489	N	0.235	0.266	0.247872288689	gnomAD-4.0.0	1.59197E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85945E-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	0.3128	likely_benign	0.2747	benign	-0.495	Destabilizing	0.961	D	0.415	neutral	N	0.48358401	None	None	N
E/C	0.9485	likely_pathogenic	0.9452	pathogenic	-0.021	Destabilizing	1.0	D	0.614	neutral	None	None	None	None	N
E/D	0.4144	ambiguous	0.387	ambiguous	-0.455	Destabilizing	0.98	D	0.496	neutral	N	0.50293294	None	None	N
E/F	0.9555	likely_pathogenic	0.9492	pathogenic	-0.446	Destabilizing	0.999	D	0.56	neutral	None	None	None	None	N
E/G	0.5405	ambiguous	0.4944	ambiguous	-0.709	Destabilizing	0.98	D	0.477	neutral	N	0.503186429	None	None	N
E/H	0.8002	likely_pathogenic	0.793	pathogenic	-0.389	Destabilizing	0.996	D	0.421	neutral	None	None	None	None	N
E/I	0.7202	likely_pathogenic	0.6582	pathogenic	0.039	Stabilizing	0.999	D	0.55	neutral	None	None	None	None	N
E/K	0.408	ambiguous	0.3584	ambiguous	0.143	Stabilizing	0.122	N	0.093	neutral	N	0.471470917	None	None	N
E/L	0.7708	likely_pathogenic	0.7295	pathogenic	0.039	Stabilizing	0.985	D	0.519	neutral	None	None	None	None	N
E/M	0.8038	likely_pathogenic	0.769	pathogenic	0.27	Stabilizing	1.0	D	0.514	neutral	None	None	None	None	N
E/N	0.6946	likely_pathogenic	0.6597	pathogenic	-0.097	Destabilizing	0.985	D	0.465	neutral	None	None	None	None	N
E/P	0.5181	ambiguous	0.4766	ambiguous	-0.118	Destabilizing	0.999	D	0.443	neutral	None	None	None	None	N
E/Q	0.2721	likely_benign	0.267	benign	-0.072	Destabilizing	0.489	N	0.235	neutral	N	0.468597308	None	None	N
E/R	0.5306	ambiguous	0.5183	ambiguous	0.304	Stabilizing	0.942	D	0.445	neutral	None	None	None	None	N
E/S	0.4988	ambiguous	0.4623	ambiguous	-0.287	Destabilizing	0.97	D	0.423	neutral	None	None	None	None	N
E/T	0.5701	likely_pathogenic	0.5044	ambiguous	-0.119	Destabilizing	0.985	D	0.465	neutral	None	None	None	None	N
E/V	0.4962	ambiguous	0.4263	ambiguous	-0.118	Destabilizing	0.994	D	0.451	neutral	N	0.501122514	None	None	N
E/W	0.9832	likely_pathogenic	0.9807	pathogenic	-0.311	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	N
E/Y	0.9113	likely_pathogenic	0.9049	pathogenic	-0.213	Destabilizing	0.999	D	0.517	neutral	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.