TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5875	17848;17849;17850	chr2:178731042;178731041;178731040	chr2:179595769;179595768;179595767
N2AB	5558	16897;16898;16899	chr2:178731042;178731041;178731040	chr2:179595769;179595768;179595767
N2A	4631	14116;14117;14118	chr2:178731042;178731041;178731040	chr2:179595769;179595768;179595767
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-42
• Domain position: 53
• Structural Position: 131
• Q(SASA): 0.9167
• 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/G	None	None	0.822	N	0.459	0.178	0.128392430309	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
D/Y	rs776136342	0.183	0.997	N	0.573	0.404	0.546306241058	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
D/Y	rs776136342	0.183	0.997	N	0.573	0.404	0.546306241058	gnomAD-4.0.0	1.59147E-06	None	None	None	None	N	None	5.66187E-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
D/A	0.2471	likely_benign	0.2452	benign	-0.196	Destabilizing	0.058	N	0.341	neutral	N	0.490553121	None	None	N
D/C	0.8241	likely_pathogenic	0.8229	pathogenic	-0.103	Destabilizing	0.998	D	0.589	neutral	None	None	None	None	N
D/E	0.1962	likely_benign	0.1782	benign	-0.26	Destabilizing	0.014	N	0.204	neutral	N	0.427925794	None	None	N
D/F	0.8624	likely_pathogenic	0.8681	pathogenic	0.104	Stabilizing	0.993	D	0.576	neutral	None	None	None	None	N
D/G	0.1651	likely_benign	0.1649	benign	-0.428	Destabilizing	0.822	D	0.459	neutral	N	0.439542724	None	None	N
D/H	0.3977	ambiguous	0.4306	ambiguous	0.35	Stabilizing	0.992	D	0.461	neutral	N	0.505349215	None	None	N
D/I	0.7648	likely_pathogenic	0.766	pathogenic	0.376	Stabilizing	0.978	D	0.568	neutral	None	None	None	None	N
D/K	0.4247	ambiguous	0.4508	ambiguous	0.367	Stabilizing	0.754	D	0.419	neutral	None	None	None	None	N
D/L	0.6913	likely_pathogenic	0.6885	pathogenic	0.376	Stabilizing	0.956	D	0.568	neutral	None	None	None	None	N
D/M	0.8418	likely_pathogenic	0.8313	pathogenic	0.355	Stabilizing	0.998	D	0.578	neutral	None	None	None	None	N
D/N	0.1055	likely_benign	0.1088	benign	-0.173	Destabilizing	0.942	D	0.391	neutral	N	0.455208396	None	None	N
D/P	0.613	likely_pathogenic	0.6212	pathogenic	0.209	Stabilizing	0.978	D	0.455	neutral	None	None	None	None	N
D/Q	0.4271	ambiguous	0.4321	ambiguous	-0.079	Destabilizing	0.915	D	0.414	neutral	None	None	None	None	N
D/R	0.476	ambiguous	0.5129	ambiguous	0.614	Stabilizing	0.956	D	0.53	neutral	None	None	None	None	N
D/S	0.1534	likely_benign	0.1525	benign	-0.247	Destabilizing	0.754	D	0.399	neutral	None	None	None	None	N
D/T	0.4268	ambiguous	0.4275	ambiguous	-0.049	Destabilizing	0.956	D	0.415	neutral	None	None	None	None	N
D/V	0.5182	ambiguous	0.5263	ambiguous	0.209	Stabilizing	0.942	D	0.537	neutral	N	0.456327678	None	None	N
D/W	0.9509	likely_pathogenic	0.9549	pathogenic	0.285	Stabilizing	0.998	D	0.635	neutral	None	None	None	None	N
D/Y	0.4747	ambiguous	0.5121	ambiguous	0.36	Stabilizing	0.997	D	0.573	neutral	N	0.461100618	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.