TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35672	107239;107240;107241	chr2:178528737;178528736;178528735	chr2:179393464;179393463;179393462
N2AB	34031	102316;102317;102318	chr2:178528737;178528736;178528735	chr2:179393464;179393463;179393462
N2A	33104	99535;99536;99537	chr2:178528737;178528736;178528735	chr2:179393464;179393463;179393462
N2B	26607	80044;80045;80046	chr2:178528737;178528736;178528735	chr2:179393464;179393463;179393462
Novex-1	26732	80419;80420;80421	chr2:178528737;178528736;178528735	chr2:179393464;179393463;179393462
Novex-2	26799	80620;80621;80622	chr2:178528737;178528736;178528735	chr2:179393464;179393463;179393462
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-167
• Domain position: 66
• Structural Position: 151
• Q(SASA): 0.3235
• 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
E/D	rs753906444	-0.663	0.822	N	0.471	0.072	0.190952846119	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
E/D	rs753906444	-0.663	0.822	N	0.471	0.072	0.190952846119	gnomAD-4.0.0	1.59256E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4339E-05	0
E/K	None	None	0.698	N	0.513	0.116	0.29385284311	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-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
E/A	0.1584	likely_benign	0.1578	benign	-0.744	Destabilizing	0.014	N	0.298	neutral	N	0.474549958	None	None	N
E/C	0.9457	likely_pathogenic	0.9362	pathogenic	-0.097	Destabilizing	0.994	D	0.645	neutral	None	None	None	None	N
E/D	0.4359	ambiguous	0.4374	ambiguous	-0.567	Destabilizing	0.822	D	0.471	neutral	N	0.476110183	None	None	N
E/F	0.8875	likely_pathogenic	0.9071	pathogenic	-0.504	Destabilizing	0.978	D	0.646	neutral	None	None	None	None	N
E/G	0.2227	likely_benign	0.2307	benign	-1.006	Destabilizing	0.698	D	0.522	neutral	N	0.4764569	None	None	N
E/H	0.6763	likely_pathogenic	0.6976	pathogenic	-0.584	Destabilizing	0.978	D	0.537	neutral	None	None	None	None	N
E/I	0.5799	likely_pathogenic	0.5863	pathogenic	-0.058	Destabilizing	0.956	D	0.641	neutral	None	None	None	None	N
E/K	0.136	likely_benign	0.1468	benign	0.099	Stabilizing	0.698	D	0.513	neutral	N	0.475243392	None	None	N
E/L	0.628	likely_pathogenic	0.6474	pathogenic	-0.058	Destabilizing	0.754	D	0.558	neutral	None	None	None	None	N
E/M	0.5765	likely_pathogenic	0.5803	pathogenic	0.319	Stabilizing	0.994	D	0.629	neutral	None	None	None	None	N
E/N	0.4934	ambiguous	0.4939	ambiguous	-0.333	Destabilizing	0.86	D	0.489	neutral	None	None	None	None	N
E/P	0.9347	likely_pathogenic	0.9495	pathogenic	-0.267	Destabilizing	0.978	D	0.593	neutral	None	None	None	None	N
E/Q	0.1378	likely_benign	0.1395	benign	-0.271	Destabilizing	0.058	N	0.148	neutral	N	0.44648071	None	None	N
E/R	0.2423	likely_benign	0.2655	benign	0.231	Stabilizing	0.754	D	0.491	neutral	None	None	None	None	N
E/S	0.2569	likely_benign	0.2571	benign	-0.536	Destabilizing	0.754	D	0.494	neutral	None	None	None	None	N
E/T	0.3149	likely_benign	0.3107	benign	-0.313	Destabilizing	0.86	D	0.527	neutral	None	None	None	None	N
E/V	0.3859	ambiguous	0.3875	ambiguous	-0.267	Destabilizing	0.698	D	0.541	neutral	N	0.476283542	None	None	N
E/W	0.9604	likely_pathogenic	0.968	pathogenic	-0.272	Destabilizing	0.998	D	0.671	neutral	None	None	None	None	N
E/Y	0.8369	likely_pathogenic	0.8541	pathogenic	-0.24	Destabilizing	0.993	D	0.639	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.