TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25881	77866;77867;77868	chr2:178568491;178568490;178568489	chr2:179433218;179433217;179433216
N2AB	24240	72943;72944;72945	chr2:178568491;178568490;178568489	chr2:179433218;179433217;179433216
N2A	23313	70162;70163;70164	chr2:178568491;178568490;178568489	chr2:179433218;179433217;179433216
N2B	16816	50671;50672;50673	chr2:178568491;178568490;178568489	chr2:179433218;179433217;179433216
Novex-1	16941	51046;51047;51048	chr2:178568491;178568490;178568489	chr2:179433218;179433217;179433216
Novex-2	17008	51247;51248;51249	chr2:178568491;178568490;178568489	chr2:179433218;179433217;179433216
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-136
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.2366
• 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/V	None	None	0.008	D	0.46	0.229	0.291694819147	gnomAD-4.0.0	1.59208E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85964E-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	0.3717	ambiguous	0.3595	ambiguous	-0.819	Destabilizing	0.989	D	0.736	prob.delet.	None	None	None	None	N
A/D	0.393	ambiguous	0.384	ambiguous	-0.33	Destabilizing	0.987	D	0.828	deleterious	None	None	None	None	N
A/E	0.3524	ambiguous	0.3401	ambiguous	-0.431	Destabilizing	0.949	D	0.805	deleterious	D	0.525229495	None	None	N
A/F	0.3252	likely_benign	0.3186	benign	-0.892	Destabilizing	0.024	N	0.643	neutral	None	None	None	None	N
A/G	0.1728	likely_benign	0.1667	benign	-0.667	Destabilizing	0.84	D	0.705	prob.neutral	N	0.509525165	None	None	N
A/H	0.5133	ambiguous	0.5131	ambiguous	-0.761	Destabilizing	0.996	D	0.777	deleterious	None	None	None	None	N
A/I	0.2109	likely_benign	0.1979	benign	-0.3	Destabilizing	0.096	N	0.491	neutral	None	None	None	None	N
A/K	0.5483	ambiguous	0.5473	ambiguous	-0.781	Destabilizing	0.961	D	0.804	deleterious	None	None	None	None	N
A/L	0.2053	likely_benign	0.1998	benign	-0.3	Destabilizing	0.415	N	0.711	prob.delet.	None	None	None	None	N
A/M	0.2143	likely_benign	0.2099	benign	-0.369	Destabilizing	0.923	D	0.787	deleterious	None	None	None	None	N
A/N	0.3519	ambiguous	0.3472	ambiguous	-0.471	Destabilizing	0.987	D	0.813	deleterious	None	None	None	None	N
A/P	0.9245	likely_pathogenic	0.9342	pathogenic	-0.333	Destabilizing	0.983	D	0.815	deleterious	D	0.549114263	None	None	N
A/Q	0.4139	ambiguous	0.408	ambiguous	-0.669	Destabilizing	0.987	D	0.8	deleterious	None	None	None	None	N
A/R	0.5203	ambiguous	0.5159	ambiguous	-0.428	Destabilizing	0.961	D	0.808	deleterious	None	None	None	None	N
A/S	0.1002	likely_benign	0.0989	benign	-0.787	Destabilizing	0.722	D	0.694	prob.neutral	D	0.522650549	None	None	N
A/T	0.0817	likely_benign	0.0808	benign	-0.789	Destabilizing	0.722	D	0.719	prob.delet.	N	0.519938318	None	None	N
A/V	0.107	likely_benign	0.1021	benign	-0.333	Destabilizing	0.008	N	0.46	neutral	D	0.525306853	None	None	N
A/W	0.786	likely_pathogenic	0.7924	pathogenic	-1.103	Destabilizing	0.996	D	0.812	deleterious	None	None	None	None	N
A/Y	0.4859	ambiguous	0.49	ambiguous	-0.719	Destabilizing	0.858	D	0.831	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.