TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7541	22846;22847;22848	chr2:178722042;178722041;178722040	chr2:179586769;179586768;179586767
N2AB	7224	21895;21896;21897	chr2:178722042;178722041;178722040	chr2:179586769;179586768;179586767
N2A	6297	19114;19115;19116	chr2:178722042;178722041;178722040	chr2:179586769;179586768;179586767
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: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-60
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.5571
• 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
A/P	rs2078459574	None	0.939	N	0.448	0.321	0.418221603839	gnomAD-4.0.0	1.30054E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.70948E-05	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	0.5861	likely_pathogenic	0.6006	pathogenic	-0.537	Destabilizing	0.02	N	0.261	neutral	None	None	None	None	I
A/D	0.2046	likely_benign	0.2128	benign	-1.071	Destabilizing	0.684	D	0.563	neutral	N	0.342774765	None	None	I
A/E	0.1931	likely_benign	0.1972	benign	-1.221	Destabilizing	0.742	D	0.445	neutral	None	None	None	None	I
A/F	0.2863	likely_benign	0.2919	benign	-1.112	Destabilizing	0.953	D	0.577	neutral	None	None	None	None	I
A/G	0.1398	likely_benign	0.1432	benign	-0.631	Destabilizing	0.684	D	0.338	neutral	N	0.490154129	None	None	I
A/H	0.483	ambiguous	0.4763	ambiguous	-0.826	Destabilizing	0.996	D	0.565	neutral	None	None	None	None	I
A/I	0.2322	likely_benign	0.2373	benign	-0.46	Destabilizing	0.91	D	0.433	neutral	None	None	None	None	I
A/K	0.5103	ambiguous	0.5111	ambiguous	-0.972	Destabilizing	0.742	D	0.447	neutral	None	None	None	None	I
A/L	0.1742	likely_benign	0.1789	benign	-0.46	Destabilizing	0.59	D	0.4	neutral	None	None	None	None	I
A/M	0.2083	likely_benign	0.2064	benign	-0.258	Destabilizing	0.996	D	0.439	neutral	None	None	None	None	I
A/N	0.2087	likely_benign	0.2091	benign	-0.454	Destabilizing	0.91	D	0.567	neutral	None	None	None	None	I
A/P	0.2572	likely_benign	0.271	benign	-0.45	Destabilizing	0.939	D	0.448	neutral	N	0.477667621	None	None	I
A/Q	0.3337	likely_benign	0.3307	benign	-0.788	Destabilizing	0.953	D	0.45	neutral	None	None	None	None	I
A/R	0.4326	ambiguous	0.4309	ambiguous	-0.434	Destabilizing	0.953	D	0.46	neutral	None	None	None	None	I
A/S	0.0753	likely_benign	0.0752	benign	-0.587	Destabilizing	0.034	N	0.184	neutral	N	0.365131549	None	None	I
A/T	0.0711	likely_benign	0.0709	benign	-0.676	Destabilizing	0.012	N	0.182	neutral	N	0.434722134	None	None	I
A/V	0.1235	likely_benign	0.127	benign	-0.45	Destabilizing	0.521	D	0.353	neutral	N	0.434356774	None	None	I
A/W	0.7107	likely_pathogenic	0.7237	pathogenic	-1.295	Destabilizing	0.996	D	0.638	neutral	None	None	None	None	I
A/Y	0.4483	ambiguous	0.4521	ambiguous	-0.965	Destabilizing	0.984	D	0.579	neutral	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.