TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28792	86599;86600;86601	chr2:178559758;178559757;178559756	chr2:179424485;179424484;179424483
N2AB	27151	81676;81677;81678	chr2:178559758;178559757;178559756	chr2:179424485;179424484;179424483
N2A	26224	78895;78896;78897	chr2:178559758;178559757;178559756	chr2:179424485;179424484;179424483
N2B	19727	59404;59405;59406	chr2:178559758;178559757;178559756	chr2:179424485;179424484;179424483
Novex-1	19852	59779;59780;59781	chr2:178559758;178559757;178559756	chr2:179424485;179424484;179424483
Novex-2	19919	59980;59981;59982	chr2:178559758;178559757;178559756	chr2:179424485;179424484;179424483
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: Ig-144
• Domain position: 38
• Structural Position: 52
• Q(SASA): 1.0089
• 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
D/Y	None	None	1.0	N	0.623	0.494	0.620746667299	gnomAD-4.0.0	2.76378E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	5.27241E-04	9.05476E-07	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
D/A	0.1723	likely_benign	0.1742	benign	0.048	Stabilizing	1.0	D	0.601	neutral	N	0.467328362	None	None	N
D/C	0.6096	likely_pathogenic	0.5994	pathogenic	-0.165	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
D/E	0.1414	likely_benign	0.1333	benign	-0.363	Destabilizing	1.0	D	0.475	neutral	N	0.453944141	None	None	N
D/F	0.5617	ambiguous	0.555	ambiguous	-0.121	Destabilizing	1.0	D	0.624	neutral	None	None	None	None	N
D/G	0.1139	likely_benign	0.1158	benign	-0.04	Destabilizing	1.0	D	0.628	neutral	N	0.421836823	None	None	N
D/H	0.3196	likely_benign	0.3209	benign	0.511	Stabilizing	1.0	D	0.619	neutral	N	0.485939596	None	None	N
D/I	0.4006	ambiguous	0.3871	ambiguous	0.209	Stabilizing	1.0	D	0.616	neutral	None	None	None	None	N
D/K	0.4221	ambiguous	0.4239	ambiguous	0.37	Stabilizing	1.0	D	0.62	neutral	None	None	None	None	N
D/L	0.41	ambiguous	0.3946	ambiguous	0.209	Stabilizing	1.0	D	0.62	neutral	None	None	None	None	N
D/M	0.5756	likely_pathogenic	0.5598	ambiguous	-0.009	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	N
D/N	0.0933	likely_benign	0.0947	benign	0.227	Stabilizing	1.0	D	0.61	neutral	N	0.472292647	None	None	N
D/P	0.772	likely_pathogenic	0.7728	pathogenic	0.173	Stabilizing	1.0	D	0.605	neutral	None	None	None	None	N
D/Q	0.3331	likely_benign	0.3285	benign	0.207	Stabilizing	1.0	D	0.625	neutral	None	None	None	None	N
D/R	0.4857	ambiguous	0.4885	ambiguous	0.584	Stabilizing	1.0	D	0.593	neutral	None	None	None	None	N
D/S	0.1295	likely_benign	0.1317	benign	0.116	Stabilizing	1.0	D	0.622	neutral	None	None	None	None	N
D/T	0.2445	likely_benign	0.2417	benign	0.189	Stabilizing	1.0	D	0.627	neutral	None	None	None	None	N
D/V	0.2458	likely_benign	0.2412	benign	0.173	Stabilizing	1.0	D	0.62	neutral	N	0.497802881	None	None	N
D/W	0.8969	likely_pathogenic	0.8969	pathogenic	-0.113	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	N
D/Y	0.2784	likely_benign	0.2744	benign	0.095	Stabilizing	1.0	D	0.623	neutral	N	0.497549391	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.