TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29315	88168;88169;88170	chr2:178557319;178557318;178557317	chr2:179422046;179422045;179422044
N2AB	27674	83245;83246;83247	chr2:178557319;178557318;178557317	chr2:179422046;179422045;179422044
N2A	26747	80464;80465;80466	chr2:178557319;178557318;178557317	chr2:179422046;179422045;179422044
N2B	20250	60973;60974;60975	chr2:178557319;178557318;178557317	chr2:179422046;179422045;179422044
Novex-1	20375	61348;61349;61350	chr2:178557319;178557318;178557317	chr2:179422046;179422045;179422044
Novex-2	20442	61549;61550;61551	chr2:178557319;178557318;178557317	chr2:179422046;179422045;179422044
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: Fn3-101
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.2487
• 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
E/Q	None	None	1.0	N	0.639	0.334	0.279776271856	gnomAD-4.0.0	1.59107E-06	None	None	None	None	I	None	5.65163E-05	0	None	0	0	None	0	0	0	0	0
E/V	None	None	1.0	N	0.831	0.516	0.379366414296	gnomAD-4.0.0	1.59105E-06	None	None	None	None	I	None	0	0	None	0	2.77485E-05	None	0	0	0	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	0.5515	ambiguous	0.5322	ambiguous	-0.942	Destabilizing	0.999	D	0.695	prob.neutral	N	0.471974215	None	None	I
E/C	0.9405	likely_pathogenic	0.9432	pathogenic	-0.73	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	I
E/D	0.8571	likely_pathogenic	0.8604	pathogenic	-1.588	Destabilizing	0.999	D	0.497	neutral	D	0.524035708	None	None	I
E/F	0.9667	likely_pathogenic	0.9579	pathogenic	-0.871	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	I
E/G	0.7761	likely_pathogenic	0.771	pathogenic	-1.316	Destabilizing	1.0	D	0.773	deleterious	N	0.506096037	None	None	I
E/H	0.9033	likely_pathogenic	0.8877	pathogenic	-1.224	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	I
E/I	0.5557	ambiguous	0.5249	ambiguous	0.089	Stabilizing	1.0	D	0.897	deleterious	None	None	None	None	I
E/K	0.4711	ambiguous	0.4468	ambiguous	-1.207	Destabilizing	0.999	D	0.563	neutral	N	0.477431944	None	None	I
E/L	0.7746	likely_pathogenic	0.7518	pathogenic	0.089	Stabilizing	1.0	D	0.86	deleterious	None	None	None	None	I
E/M	0.6965	likely_pathogenic	0.6709	pathogenic	0.649	Stabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
E/N	0.8872	likely_pathogenic	0.8853	pathogenic	-1.489	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
E/P	0.9986	likely_pathogenic	0.9987	pathogenic	-0.234	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
E/Q	0.2232	likely_benign	0.2276	benign	-1.292	Destabilizing	1.0	D	0.639	neutral	N	0.476671476	None	None	I
E/R	0.6573	likely_pathogenic	0.6562	pathogenic	-1.105	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	I
E/S	0.7144	likely_pathogenic	0.6921	pathogenic	-1.943	Destabilizing	0.999	D	0.601	neutral	None	None	None	None	I
E/T	0.6669	likely_pathogenic	0.6345	pathogenic	-1.62	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	I
E/V	0.3508	ambiguous	0.3236	benign	-0.234	Destabilizing	1.0	D	0.831	deleterious	N	0.47497038	None	None	I
E/W	0.9921	likely_pathogenic	0.9906	pathogenic	-0.936	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
E/Y	0.9601	likely_pathogenic	0.9532	pathogenic	-0.702	Destabilizing	1.0	D	0.86	deleterious	None	None	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.