TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29264	88015;88016;88017	chr2:178557472;178557471;178557470	chr2:179422199;179422198;179422197
N2AB	27623	83092;83093;83094	chr2:178557472;178557471;178557470	chr2:179422199;179422198;179422197
N2A	26696	80311;80312;80313	chr2:178557472;178557471;178557470	chr2:179422199;179422198;179422197
N2B	20199	60820;60821;60822	chr2:178557472;178557471;178557470	chr2:179422199;179422198;179422197
Novex-1	20324	61195;61196;61197	chr2:178557472;178557471;178557470	chr2:179422199;179422198;179422197
Novex-2	20391	61396;61397;61398	chr2:178557472;178557471;178557470	chr2:179422199;179422198;179422197
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-101
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.3417
• Predicted PPI site: I

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
N/K	None	None	0.379	N	0.349	0.134	0.16115917748	gnomAD-4.0.0	6.84173E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99421E-07	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
N/A	0.3321	likely_benign	0.4366	ambiguous	-0.559	Destabilizing	0.25	N	0.471	neutral	None	None	None	None	I
N/C	0.4003	ambiguous	0.5339	ambiguous	0.291	Stabilizing	0.992	D	0.525	neutral	None	None	None	None	I
N/D	0.0673	likely_benign	0.076	benign	-0.391	Destabilizing	0.001	N	0.09	neutral	N	0.350532164	None	None	I
N/E	0.6296	likely_pathogenic	0.7211	pathogenic	-0.411	Destabilizing	0.25	N	0.361	neutral	None	None	None	None	I
N/F	0.8086	likely_pathogenic	0.8662	pathogenic	-0.946	Destabilizing	0.92	D	0.517	neutral	None	None	None	None	I
N/G	0.3387	likely_benign	0.4489	ambiguous	-0.747	Destabilizing	0.25	N	0.379	neutral	None	None	None	None	I
N/H	0.2343	likely_benign	0.3119	benign	-0.893	Destabilizing	0.896	D	0.47	neutral	N	0.511611545	None	None	I
N/I	0.5839	likely_pathogenic	0.6782	pathogenic	-0.141	Destabilizing	0.896	D	0.528	neutral	N	0.511958261	None	None	I
N/K	0.6606	likely_pathogenic	0.7515	pathogenic	0.091	Stabilizing	0.379	N	0.349	neutral	N	0.510744753	None	None	I
N/L	0.4959	ambiguous	0.6081	pathogenic	-0.141	Destabilizing	0.85	D	0.491	neutral	None	None	None	None	I
N/M	0.639	likely_pathogenic	0.7331	pathogenic	0.526	Stabilizing	0.992	D	0.507	neutral	None	None	None	None	I
N/P	0.699	likely_pathogenic	0.7699	pathogenic	-0.255	Destabilizing	0.92	D	0.493	neutral	None	None	None	None	I
N/Q	0.6204	likely_pathogenic	0.7176	pathogenic	-0.567	Destabilizing	0.85	D	0.411	neutral	None	None	None	None	I
N/R	0.6566	likely_pathogenic	0.7502	pathogenic	0.192	Stabilizing	0.85	D	0.424	neutral	None	None	None	None	I
N/S	0.0724	likely_benign	0.0913	benign	-0.241	Destabilizing	0.016	N	0.131	neutral	N	0.483307435	None	None	I
N/T	0.1552	likely_benign	0.1923	benign	-0.113	Destabilizing	0.379	N	0.326	neutral	N	0.474053234	None	None	I
N/V	0.4623	ambiguous	0.5797	pathogenic	-0.255	Destabilizing	0.85	D	0.491	neutral	None	None	None	None	I
N/W	0.9295	likely_pathogenic	0.9544	pathogenic	-0.846	Destabilizing	0.992	D	0.612	neutral	None	None	None	None	I
N/Y	0.4025	ambiguous	0.4851	ambiguous	-0.578	Destabilizing	0.963	D	0.514	neutral	N	0.494170301	None	None	I

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.