TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29119	87580;87581;87582	chr2:178557999;178557998;178557997	chr2:179422726;179422725;179422724
N2AB	27478	82657;82658;82659	chr2:178557999;178557998;178557997	chr2:179422726;179422725;179422724
N2A	26551	79876;79877;79878	chr2:178557999;178557998;178557997	chr2:179422726;179422725;179422724
N2B	20054	60385;60386;60387	chr2:178557999;178557998;178557997	chr2:179422726;179422725;179422724
Novex-1	20179	60760;60761;60762	chr2:178557999;178557998;178557997	chr2:179422726;179422725;179422724
Novex-2	20246	60961;60962;60963	chr2:178557999;178557998;178557997	chr2:179422726;179422725;179422724
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-145
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.0786
• 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
A/P	None	None	1.0	D	0.887	0.734	0.682284130214	gnomAD-4.0.0	1.59155E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8578E-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
A/C	0.6459	likely_pathogenic	0.5961	pathogenic	-1.124	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
A/D	0.9967	likely_pathogenic	0.9966	pathogenic	-1.695	Destabilizing	1.0	D	0.896	deleterious	D	0.578869977	None	None	N
A/E	0.9901	likely_pathogenic	0.9895	pathogenic	-1.774	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
A/F	0.898	likely_pathogenic	0.8694	pathogenic	-1.334	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
A/G	0.3528	ambiguous	0.3779	ambiguous	-1.107	Destabilizing	1.0	D	0.583	neutral	D	0.562214843	None	None	N
A/H	0.9941	likely_pathogenic	0.9934	pathogenic	-1.206	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
A/I	0.4859	ambiguous	0.4106	ambiguous	-0.594	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
A/K	0.9969	likely_pathogenic	0.9967	pathogenic	-1.17	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
A/L	0.3825	ambiguous	0.3324	benign	-0.594	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
A/M	0.5549	ambiguous	0.4997	ambiguous	-0.445	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
A/N	0.988	likely_pathogenic	0.9875	pathogenic	-0.957	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
A/P	0.9893	likely_pathogenic	0.9888	pathogenic	-0.668	Destabilizing	1.0	D	0.887	deleterious	D	0.578668173	None	None	N
A/Q	0.983	likely_pathogenic	0.9809	pathogenic	-1.25	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
A/R	0.9914	likely_pathogenic	0.9912	pathogenic	-0.718	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
A/S	0.4244	ambiguous	0.4201	ambiguous	-1.198	Destabilizing	1.0	D	0.579	neutral	D	0.578264564	None	None	N
A/T	0.3249	likely_benign	0.2836	benign	-1.204	Destabilizing	1.0	D	0.783	deleterious	D	0.57806276	None	None	N
A/V	0.2037	likely_benign	0.1586	benign	-0.668	Destabilizing	1.0	D	0.655	neutral	D	0.524947067	None	None	N
A/W	0.9952	likely_pathogenic	0.9943	pathogenic	-1.573	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
A/Y	0.9778	likely_pathogenic	0.974	pathogenic	-1.195	Destabilizing	1.0	D	0.913	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.