TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5811	17656;17657;17658	chr2:178731335;178731334;178731333	chr2:179596062;179596061;179596060
N2AB	5494	16705;16706;16707	chr2:178731335;178731334;178731333	chr2:179596062;179596061;179596060
N2A	4567	13924;13925;13926	chr2:178731335;178731334;178731333	chr2:179596062;179596061;179596060
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-41
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.2276
• 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/K	None	None	0.959	N	0.379	0.262	0.299086750705	gnomAD-4.0.0	2.05267E-06	None	None	None	None	I	None	2.98846E-05	0	None	0	0	None	1.87336E-05	0	8.99486E-07	0	0
Q/P	rs776791851	-0.039	0.998	N	0.531	0.521	0.421550847248	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
Q/P	rs776791851	-0.039	0.998	N	0.531	0.521	0.421550847248	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
Q/P	rs776791851	-0.039	0.998	N	0.531	0.521	0.421550847248	gnomAD-4.0.0	6.57082E-06	None	None	None	None	I	None	2.41161E-05	0	None	0	0	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	0.2716	likely_benign	0.2717	benign	-0.726	Destabilizing	0.864	D	0.411	neutral	None	None	None	None	I
Q/C	0.733	likely_pathogenic	0.7402	pathogenic	-0.07	Destabilizing	1.0	D	0.566	neutral	None	None	None	None	I
Q/D	0.6087	likely_pathogenic	0.6027	pathogenic	-0.346	Destabilizing	0.969	D	0.387	neutral	None	None	None	None	I
Q/E	0.1184	likely_benign	0.1188	benign	-0.236	Destabilizing	0.906	D	0.355	neutral	N	0.465255684	None	None	I
Q/F	0.7917	likely_pathogenic	0.8008	pathogenic	-0.281	Destabilizing	0.995	D	0.583	neutral	None	None	None	None	I
Q/G	0.4074	ambiguous	0.4241	ambiguous	-1.092	Destabilizing	0.969	D	0.507	neutral	None	None	None	None	I
Q/H	0.3374	likely_benign	0.3678	ambiguous	-0.737	Destabilizing	0.998	D	0.476	neutral	N	0.483517191	None	None	I
Q/I	0.4657	ambiguous	0.4798	ambiguous	0.217	Stabilizing	0.939	D	0.555	neutral	None	None	None	None	I
Q/K	0.1684	likely_benign	0.1694	benign	-0.375	Destabilizing	0.959	D	0.379	neutral	N	0.501965846	None	None	I
Q/L	0.1958	likely_benign	0.2086	benign	0.217	Stabilizing	0.921	D	0.475	neutral	D	0.52572814	None	None	I
Q/M	0.4573	ambiguous	0.465	ambiguous	0.495	Stabilizing	0.995	D	0.481	neutral	None	None	None	None	I
Q/N	0.4778	ambiguous	0.481	ambiguous	-0.877	Destabilizing	0.969	D	0.451	neutral	None	None	None	None	I
Q/P	0.763	likely_pathogenic	0.7844	pathogenic	-0.067	Destabilizing	0.998	D	0.531	neutral	N	0.49529157	None	None	I
Q/R	0.1632	likely_benign	0.166	benign	-0.289	Destabilizing	0.979	D	0.499	neutral	N	0.506526304	None	None	I
Q/S	0.3244	likely_benign	0.3157	benign	-1.027	Destabilizing	0.546	D	0.193	neutral	None	None	None	None	I
Q/T	0.2729	likely_benign	0.2711	benign	-0.721	Destabilizing	0.969	D	0.427	neutral	None	None	None	None	I
Q/V	0.2971	likely_benign	0.3087	benign	-0.067	Destabilizing	0.293	N	0.374	neutral	None	None	None	None	I
Q/W	0.7326	likely_pathogenic	0.7556	pathogenic	-0.129	Destabilizing	1.0	D	0.621	neutral	None	None	None	None	I
Q/Y	0.6006	likely_pathogenic	0.6227	pathogenic	0.066	Stabilizing	0.999	D	0.535	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.