TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28176	84751;84752;84753	chr2:178561606;178561605;178561604	chr2:179426333;179426332;179426331
N2AB	26535	79828;79829;79830	chr2:178561606;178561605;178561604	chr2:179426333;179426332;179426331
N2A	25608	77047;77048;77049	chr2:178561606;178561605;178561604	chr2:179426333;179426332;179426331
N2B	19111	57556;57557;57558	chr2:178561606;178561605;178561604	chr2:179426333;179426332;179426331
Novex-1	19236	57931;57932;57933	chr2:178561606;178561605;178561604	chr2:179426333;179426332;179426331
Novex-2	19303	58132;58133;58134	chr2:178561606;178561605;178561604	chr2:179426333;179426332;179426331
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Fn3-93
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.6316
• 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
Q/P	None	None	0.856	N	0.562	0.281	0.344251166708	gnomAD-4.0.0	1.59298E-06	None	None	None	None	I	None	0	0	None	0	2.78226E-05	None	0	0	0	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
Q/A	0.1998	likely_benign	0.1885	benign	-0.242	Destabilizing	0.345	N	0.393	neutral	None	None	None	None	I
Q/C	0.6151	likely_pathogenic	0.6161	pathogenic	0.142	Stabilizing	0.991	D	0.44	neutral	None	None	None	None	I
Q/D	0.2353	likely_benign	0.2148	benign	0.053	Stabilizing	0.209	N	0.425	neutral	None	None	None	None	I
Q/E	0.0809	likely_benign	0.0809	benign	0.029	Stabilizing	0.285	N	0.315	neutral	N	0.391186708	None	None	I
Q/F	0.6927	likely_pathogenic	0.6709	pathogenic	-0.433	Destabilizing	0.901	D	0.455	neutral	None	None	None	None	I
Q/G	0.2254	likely_benign	0.2027	benign	-0.433	Destabilizing	0.002	N	0.277	neutral	None	None	None	None	I
Q/H	0.1505	likely_benign	0.1483	benign	-0.319	Destabilizing	0.003	N	0.237	neutral	N	0.43157468	None	None	I
Q/I	0.4787	ambiguous	0.474	ambiguous	0.172	Stabilizing	0.901	D	0.477	neutral	None	None	None	None	I
Q/K	0.1166	likely_benign	0.1149	benign	0.084	Stabilizing	0.285	N	0.409	neutral	N	0.391706783	None	None	I
Q/L	0.1448	likely_benign	0.1451	benign	0.172	Stabilizing	0.491	N	0.494	neutral	N	0.466975333	None	None	I
Q/M	0.3537	ambiguous	0.3618	ambiguous	0.412	Stabilizing	0.965	D	0.463	neutral	None	None	None	None	I
Q/N	0.1608	likely_benign	0.1515	benign	-0.279	Destabilizing	0.001	N	0.176	neutral	None	None	None	None	I
Q/P	0.1293	likely_benign	0.1216	benign	0.063	Stabilizing	0.856	D	0.562	neutral	N	0.479963273	None	None	I
Q/R	0.1389	likely_benign	0.1321	benign	0.227	Stabilizing	0.491	N	0.38	neutral	N	0.449467008	None	None	I
Q/S	0.199	likely_benign	0.1838	benign	-0.276	Destabilizing	0.209	N	0.356	neutral	None	None	None	None	I
Q/T	0.1934	likely_benign	0.19	benign	-0.14	Destabilizing	0.561	D	0.457	neutral	None	None	None	None	I
Q/V	0.2921	likely_benign	0.2944	benign	0.063	Stabilizing	0.722	D	0.54	neutral	None	None	None	None	I
Q/W	0.5631	ambiguous	0.5508	ambiguous	-0.397	Destabilizing	0.991	D	0.455	neutral	None	None	None	None	I
Q/Y	0.4099	ambiguous	0.4007	ambiguous	-0.142	Destabilizing	0.692	D	0.563	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.