TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25990	78193;78194;78195	chr2:178568164;178568163;178568162	chr2:179432891;179432890;179432889
N2AB	24349	73270;73271;73272	chr2:178568164;178568163;178568162	chr2:179432891;179432890;179432889
N2A	23422	70489;70490;70491	chr2:178568164;178568163;178568162	chr2:179432891;179432890;179432889
N2B	16925	50998;50999;51000	chr2:178568164;178568163;178568162	chr2:179432891;179432890;179432889
Novex-1	17050	51373;51374;51375	chr2:178568164;178568163;178568162	chr2:179432891;179432890;179432889
Novex-2	17117	51574;51575;51576	chr2:178568164;178568163;178568162	chr2:179432891;179432890;179432889
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: Fn3-77
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.4117
• 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/D	rs532095547	-0.8	0.489	N	0.449	0.166	0.254244900254	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/D	rs532095547	-0.8	0.489	N	0.449	0.166	0.254244900254	gnomAD-4.0.0	6.84301E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15939E-05	0
E/G	None	None	0.321	N	0.593	0.205	0.257292322809	gnomAD-4.0.0	1.59178E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43291E-05	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	0.1147	likely_benign	0.1418	benign	-0.441	Destabilizing	0.006	N	0.286	neutral	N	0.448517284	None	None	I
E/C	0.7161	likely_pathogenic	0.7777	pathogenic	-0.03	Destabilizing	0.944	D	0.829	deleterious	None	None	None	None	I
E/D	0.3555	ambiguous	0.3538	ambiguous	-0.303	Destabilizing	0.489	N	0.449	neutral	N	0.48737899	None	None	I
E/F	0.7475	likely_pathogenic	0.8165	pathogenic	-0.324	Destabilizing	0.687	D	0.822	deleterious	None	None	None	None	I
E/G	0.3002	likely_benign	0.3382	benign	-0.639	Destabilizing	0.321	N	0.593	neutral	N	0.487125501	None	None	I
E/H	0.697	likely_pathogenic	0.7679	pathogenic	-0.158	Destabilizing	0.981	D	0.491	neutral	None	None	None	None	I
E/I	0.1307	likely_benign	0.176	benign	0.047	Stabilizing	0.275	N	0.6	neutral	None	None	None	None	I
E/K	0.2261	likely_benign	0.2918	benign	0.312	Stabilizing	0.489	N	0.492	neutral	N	0.475917316	None	None	I
E/L	0.2469	likely_benign	0.3078	benign	0.047	Stabilizing	0.239	N	0.599	neutral	None	None	None	None	I
E/M	0.265	likely_benign	0.3363	benign	0.192	Stabilizing	0.892	D	0.779	deleterious	None	None	None	None	I
E/N	0.4375	ambiguous	0.4996	ambiguous	0.008	Stabilizing	0.931	D	0.507	neutral	None	None	None	None	I
E/P	0.2825	likely_benign	0.3339	benign	-0.096	Destabilizing	0.817	D	0.557	neutral	None	None	None	None	I
E/Q	0.1621	likely_benign	0.2027	benign	0.039	Stabilizing	0.911	D	0.523	neutral	N	0.464590701	None	None	I
E/R	0.4058	ambiguous	0.5077	ambiguous	0.481	Stabilizing	0.817	D	0.5	neutral	None	None	None	None	I
E/S	0.2812	likely_benign	0.3395	benign	-0.165	Destabilizing	0.239	N	0.433	neutral	None	None	None	None	I
E/T	0.1839	likely_benign	0.2347	benign	-0.001	Destabilizing	0.239	N	0.637	neutral	None	None	None	None	I
E/V	0.0744	likely_benign	0.103	benign	-0.096	Destabilizing	0.001	N	0.379	neutral	N	0.421946759	None	None	I
E/W	0.9556	likely_pathogenic	0.9714	pathogenic	-0.163	Destabilizing	0.981	D	0.796	deleterious	None	None	None	None	I
E/Y	0.6909	likely_pathogenic	0.7541	pathogenic	-0.08	Destabilizing	0.817	D	0.828	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.