TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6562	19909;19910;19911	chr2:178728140;178728139;178728138	chr2:179592867;179592866;179592865
N2AB	6245	18958;18959;18960	chr2:178728140;178728139;178728138	chr2:179592867;179592866;179592865
N2A	5318	16177;16178;16179	chr2:178728140;178728139;178728138	chr2:179592867;179592866;179592865
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-49
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.234
• 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/V	None	None	0.012	N	0.454	0.129	0.376570364461	gnomAD-4.0.0	4.87976E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.45395E-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	0.0651	likely_benign	0.0556	benign	-0.526	Destabilizing	None	N	0.195	neutral	N	0.460079151	None	None	N
D/C	0.4178	ambiguous	0.4869	ambiguous	-0.168	Destabilizing	None	N	0.303	neutral	None	None	None	None	N
D/E	0.1759	likely_benign	0.1818	benign	-0.602	Destabilizing	None	N	0.083	neutral	D	0.527016219	None	None	N
D/F	0.4334	ambiguous	0.4464	ambiguous	0.006	Stabilizing	0.356	N	0.561	neutral	None	None	None	None	N
D/G	0.1412	likely_benign	0.1495	benign	-0.896	Destabilizing	None	N	0.114	neutral	N	0.51545974	None	None	N
D/H	0.1927	likely_benign	0.2201	benign	-0.25	Destabilizing	0.171	N	0.426	neutral	N	0.510851384	None	None	N
D/I	0.24	likely_benign	0.2563	benign	0.456	Stabilizing	0.072	N	0.609	neutral	None	None	None	None	N
D/K	0.2531	likely_benign	0.2748	benign	-0.172	Destabilizing	None	N	0.145	neutral	None	None	None	None	N
D/L	0.2889	likely_benign	0.2991	benign	0.456	Stabilizing	0.016	N	0.446	neutral	None	None	None	None	N
D/M	0.4227	ambiguous	0.4518	ambiguous	0.841	Stabilizing	0.356	N	0.515	neutral	None	None	None	None	N
D/N	0.0779	likely_benign	0.0964	benign	-0.707	Destabilizing	None	N	0.107	neutral	N	0.489099825	None	None	N
D/P	0.8756	likely_pathogenic	0.8919	pathogenic	0.154	Stabilizing	0.072	N	0.476	neutral	None	None	None	None	N
D/Q	0.2561	likely_benign	0.2745	benign	-0.558	Destabilizing	0.038	N	0.309	neutral	None	None	None	None	N
D/R	0.2668	likely_benign	0.2801	benign	0.012	Stabilizing	0.038	N	0.543	neutral	None	None	None	None	N
D/S	0.0729	likely_benign	0.0759	benign	-0.968	Destabilizing	0.007	N	0.235	neutral	None	None	None	None	N
D/T	0.1221	likely_benign	0.1237	benign	-0.656	Destabilizing	0.016	N	0.403	neutral	None	None	None	None	N
D/V	0.1318	likely_benign	0.1356	benign	0.154	Stabilizing	0.012	N	0.454	neutral	N	0.483052011	None	None	N
D/W	0.8418	likely_pathogenic	0.8612	pathogenic	0.244	Stabilizing	0.864	D	0.509	neutral	None	None	None	None	N
D/Y	0.1679	likely_benign	0.1787	benign	0.286	Stabilizing	0.295	N	0.555	neutral	D	0.533817484	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.