TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7176	21751;21752;21753	chr2:178723574;178723573;178723572	chr2:179588301;179588300;179588299
N2AB	6859	20800;20801;20802	chr2:178723574;178723573;178723572	chr2:179588301;179588300;179588299
N2A	5932	18019;18020;18021	chr2:178723574;178723573;178723572	chr2:179588301;179588300;179588299
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-56
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.6181
• 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/G	rs2078807925	None	1.0	N	0.676	0.589	0.565318601174	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	0.2001	likely_benign	0.2065	benign	-0.63	Destabilizing	0.999	D	0.688	prob.neutral	N	0.504254792	None	None	N
E/C	0.9024	likely_pathogenic	0.9032	pathogenic	-0.428	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
E/D	0.3544	ambiguous	0.3709	ambiguous	-0.687	Destabilizing	0.999	D	0.497	neutral	N	0.483895584	None	None	N
E/F	0.8503	likely_pathogenic	0.8551	pathogenic	0.053	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
E/G	0.2686	likely_benign	0.2876	benign	-0.949	Destabilizing	1.0	D	0.676	prob.neutral	N	0.510637574	None	None	N
E/H	0.6398	likely_pathogenic	0.6451	pathogenic	0.175	Stabilizing	1.0	D	0.659	neutral	None	None	None	None	N
E/I	0.4336	ambiguous	0.4456	ambiguous	0.225	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
E/K	0.1755	likely_benign	0.1807	benign	-0.148	Destabilizing	0.999	D	0.643	neutral	N	0.487098362	None	None	N
E/L	0.4439	ambiguous	0.4537	ambiguous	0.225	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
E/M	0.5044	ambiguous	0.512	ambiguous	0.337	Stabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
E/N	0.4687	ambiguous	0.4827	ambiguous	-0.786	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
E/P	0.419	ambiguous	0.4287	ambiguous	-0.039	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/Q	0.1576	likely_benign	0.1572	benign	-0.66	Destabilizing	1.0	D	0.629	neutral	N	0.486719968	None	None	N
E/R	0.3319	likely_benign	0.3375	benign	0.267	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/S	0.3617	ambiguous	0.3768	ambiguous	-0.998	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
E/T	0.3882	ambiguous	0.3967	ambiguous	-0.725	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
E/V	0.248	likely_benign	0.2537	benign	-0.039	Destabilizing	1.0	D	0.719	prob.delet.	N	0.485847822	None	None	N
E/W	0.9483	likely_pathogenic	0.9499	pathogenic	0.366	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
E/Y	0.7694	likely_pathogenic	0.7755	pathogenic	0.33	Stabilizing	1.0	D	0.692	prob.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.