TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22868	68827;68828;68829	chr2:178577824;178577823;178577822	chr2:179442551;179442550;179442549
N2AB	21227	63904;63905;63906	chr2:178577824;178577823;178577822	chr2:179442551;179442550;179442549
N2A	20300	61123;61124;61125	chr2:178577824;178577823;178577822	chr2:179442551;179442550;179442549
N2B	13803	41632;41633;41634	chr2:178577824;178577823;178577822	chr2:179442551;179442550;179442549
Novex-1	13928	42007;42008;42009	chr2:178577824;178577823;178577822	chr2:179442551;179442550;179442549
Novex-2	13995	42208;42209;42210	chr2:178577824;178577823;178577822	chr2:179442551;179442550;179442549
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-54
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.3967
• 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
D/E	rs750368181	-0.268	1.0	N	0.44	0.438	0.410868550352	gnomAD-2.1.1	4.06E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.32E-05	None	0	0	0
D/E	rs750368181	-0.268	1.0	N	0.44	0.438	0.410868550352	gnomAD-4.0.0	6.85305E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.16499E-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
D/A	0.6064	likely_pathogenic	0.6823	pathogenic	-0.685	Destabilizing	1.0	D	0.757	deleterious	N	0.494045397	None	None	I
D/C	0.909	likely_pathogenic	0.9311	pathogenic	-0.332	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	I
D/E	0.7309	likely_pathogenic	0.8057	pathogenic	-0.63	Destabilizing	1.0	D	0.44	neutral	N	0.50224815	None	None	I
D/F	0.9336	likely_pathogenic	0.9517	pathogenic	-0.204	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
D/G	0.6016	likely_pathogenic	0.6719	pathogenic	-1.084	Destabilizing	1.0	D	0.742	deleterious	D	0.533420685	None	None	I
D/H	0.7162	likely_pathogenic	0.7808	pathogenic	-0.599	Destabilizing	1.0	D	0.697	prob.neutral	N	0.51768306	None	None	I
D/I	0.8662	likely_pathogenic	0.9029	pathogenic	0.39	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
D/K	0.8743	likely_pathogenic	0.9194	pathogenic	-0.698	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
D/L	0.8324	likely_pathogenic	0.8787	pathogenic	0.39	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
D/M	0.9332	likely_pathogenic	0.9522	pathogenic	0.926	Stabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
D/N	0.1354	likely_benign	0.1826	benign	-1.117	Destabilizing	1.0	D	0.743	deleterious	N	0.483271749	None	None	I
D/P	0.9308	likely_pathogenic	0.953	pathogenic	0.057	Stabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
D/Q	0.8325	likely_pathogenic	0.8757	pathogenic	-0.912	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
D/R	0.8603	likely_pathogenic	0.902	pathogenic	-0.557	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	I
D/S	0.2568	likely_benign	0.3193	benign	-1.484	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
D/T	0.3743	ambiguous	0.4591	ambiguous	-1.148	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	I
D/V	0.7125	likely_pathogenic	0.7818	pathogenic	0.057	Stabilizing	1.0	D	0.759	deleterious	N	0.51553024	None	None	I
D/W	0.9868	likely_pathogenic	0.9895	pathogenic	-0.057	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
D/Y	0.6925	likely_pathogenic	0.7531	pathogenic	0.023	Stabilizing	1.0	D	0.697	prob.neutral	D	0.55629788	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.