TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24178	72757;72758;72759	chr2:178573600;178573599;178573598	chr2:179438327;179438326;179438325
N2AB	22537	67834;67835;67836	chr2:178573600;178573599;178573598	chr2:179438327;179438326;179438325
N2A	21610	65053;65054;65055	chr2:178573600;178573599;178573598	chr2:179438327;179438326;179438325
N2B	15113	45562;45563;45564	chr2:178573600;178573599;178573598	chr2:179438327;179438326;179438325
Novex-1	15238	45937;45938;45939	chr2:178573600;178573599;178573598	chr2:179438327;179438326;179438325
Novex-2	15305	46138;46139;46140	chr2:178573600;178573599;178573598	chr2:179438327;179438326;179438325
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: Fn3-63
• Domain position: 57
• Structural Position: 83
• Q(SASA): 0.8736
• 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
Q/H	None	None	0.979	N	0.396	0.208	0.219573609325	gnomAD-4.0.0	7.42763E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.80623E-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
Q/A	0.1039	likely_benign	0.1003	benign	-0.128	Destabilizing	0.373	N	0.396	neutral	None	None	None	None	N
Q/C	0.4912	ambiguous	0.4933	ambiguous	-0.057	Destabilizing	0.996	D	0.361	neutral	None	None	None	None	N
Q/D	0.2604	likely_benign	0.2511	benign	0.068	Stabilizing	0.742	D	0.383	neutral	None	None	None	None	N
Q/E	0.0754	likely_benign	0.0728	benign	0.058	Stabilizing	0.472	N	0.337	neutral	N	0.435209631	None	None	N
Q/F	0.585	likely_pathogenic	0.5431	ambiguous	-0.315	Destabilizing	0.91	D	0.36	neutral	None	None	None	None	N
Q/G	0.201	likely_benign	0.186	benign	-0.314	Destabilizing	0.742	D	0.429	neutral	None	None	None	None	N
Q/H	0.1774	likely_benign	0.1619	benign	-0.024	Destabilizing	0.979	D	0.396	neutral	N	0.494623294	None	None	N
Q/I	0.2615	likely_benign	0.2481	benign	0.276	Stabilizing	0.835	D	0.357	neutral	None	None	None	None	N
Q/K	0.0883	likely_benign	0.0866	benign	0.03	Stabilizing	0.684	D	0.346	neutral	N	0.431593323	None	None	N
Q/L	0.1052	likely_benign	0.1015	benign	0.276	Stabilizing	0.007	N	0.22	neutral	D	0.523868766	None	None	N
Q/M	0.231	likely_benign	0.2289	benign	0.204	Stabilizing	0.91	D	0.401	neutral	None	None	None	None	N
Q/N	0.1923	likely_benign	0.1807	benign	-0.405	Destabilizing	0.953	D	0.368	neutral	None	None	None	None	N
Q/P	0.0649	likely_benign	0.0624	benign	0.17	Stabilizing	0.003	N	0.169	neutral	N	0.442578321	None	None	N
Q/R	0.1056	likely_benign	0.1005	benign	0.226	Stabilizing	0.815	D	0.383	neutral	N	0.442906395	None	None	N
Q/S	0.1366	likely_benign	0.1324	benign	-0.38	Destabilizing	0.742	D	0.342	neutral	None	None	None	None	N
Q/T	0.1116	likely_benign	0.1074	benign	-0.236	Destabilizing	0.742	D	0.427	neutral	None	None	None	None	N
Q/V	0.1547	likely_benign	0.1508	benign	0.17	Stabilizing	0.59	D	0.414	neutral	None	None	None	None	N
Q/W	0.5056	ambiguous	0.4462	ambiguous	-0.336	Destabilizing	0.996	D	0.407	neutral	None	None	None	None	N
Q/Y	0.3896	ambiguous	0.3726	ambiguous	-0.06	Destabilizing	0.953	D	0.409	neutral	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.