TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26172	78739;78740;78741	chr2:178567618;178567617;178567616	chr2:179432345;179432344;179432343
N2AB	24531	73816;73817;73818	chr2:178567618;178567617;178567616	chr2:179432345;179432344;179432343
N2A	23604	71035;71036;71037	chr2:178567618;178567617;178567616	chr2:179432345;179432344;179432343
N2B	17107	51544;51545;51546	chr2:178567618;178567617;178567616	chr2:179432345;179432344;179432343
Novex-1	17232	51919;51920;51921	chr2:178567618;178567617;178567616	chr2:179432345;179432344;179432343
Novex-2	17299	52120;52121;52122	chr2:178567618;178567617;178567616	chr2:179432345;179432344;179432343
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-78
• Domain position: 85
• Structural Position: 117
• Q(SASA): 0.3992
• 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
I/V	None	None	None	N	0.239	0.062	0.167679373172	gnomAD-4.0.0	1.59552E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.03122E-05

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
I/A	0.379	ambiguous	0.3169	benign	-1.021	Destabilizing	0.016	N	0.506	neutral	None	None	None	None	I
I/C	0.6561	likely_pathogenic	0.596	pathogenic	-0.709	Destabilizing	0.676	D	0.638	neutral	None	None	None	None	I
I/D	0.8168	likely_pathogenic	0.7606	pathogenic	-0.369	Destabilizing	0.356	N	0.684	prob.neutral	None	None	None	None	I
I/E	0.7181	likely_pathogenic	0.6627	pathogenic	-0.448	Destabilizing	0.356	N	0.689	prob.neutral	None	None	None	None	I
I/F	0.1144	likely_benign	0.1056	benign	-0.97	Destabilizing	None	N	0.331	neutral	None	None	None	None	I
I/G	0.703	likely_pathogenic	0.6265	pathogenic	-1.232	Destabilizing	0.136	N	0.677	prob.neutral	None	None	None	None	I
I/H	0.5597	ambiguous	0.5062	ambiguous	-0.491	Destabilizing	0.356	N	0.668	neutral	None	None	None	None	I
I/K	0.57	likely_pathogenic	0.4872	ambiguous	-0.521	Destabilizing	0.295	N	0.685	prob.neutral	N	0.472214477	None	None	I
I/L	0.0928	likely_benign	0.0821	benign	-0.571	Destabilizing	None	N	0.252	neutral	N	0.448792217	None	None	I
I/M	0.1049	likely_benign	0.0973	benign	-0.422	Destabilizing	0.171	N	0.655	neutral	N	0.51419049	None	None	I
I/N	0.3759	ambiguous	0.33	benign	-0.246	Destabilizing	0.628	D	0.68	prob.neutral	None	None	None	None	I
I/P	0.7714	likely_pathogenic	0.704	pathogenic	-0.687	Destabilizing	0.628	D	0.681	prob.neutral	None	None	None	None	I
I/Q	0.5533	ambiguous	0.4819	ambiguous	-0.505	Destabilizing	0.628	D	0.667	neutral	None	None	None	None	I
I/R	0.4994	ambiguous	0.4107	ambiguous	0.08	Stabilizing	0.295	N	0.68	prob.neutral	N	0.491505631	None	None	I
I/S	0.3614	ambiguous	0.3179	benign	-0.786	Destabilizing	0.072	N	0.665	neutral	None	None	None	None	I
I/T	0.2892	likely_benign	0.248	benign	-0.75	Destabilizing	0.029	N	0.565	neutral	N	0.500047757	None	None	I
I/V	0.0633	likely_benign	0.0625	benign	-0.687	Destabilizing	None	N	0.239	neutral	N	0.431899967	None	None	I
I/W	0.7192	likely_pathogenic	0.6635	pathogenic	-0.951	Destabilizing	0.864	D	0.669	neutral	None	None	None	None	I
I/Y	0.4459	ambiguous	0.4099	ambiguous	-0.706	Destabilizing	0.001	N	0.429	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.