TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14743	44452;44453;44454	chr2:178630295;178630294;178630293	chr2:179495022;179495021;179495020
N2AB	13102	39529;39530;39531	chr2:178630295;178630294;178630293	chr2:179495022;179495021;179495020
N2A	12175	36748;36749;36750	chr2:178630295;178630294;178630293	chr2:179495022;179495021;179495020
N2B	5678	17257;17258;17259	chr2:178630295;178630294;178630293	chr2:179495022;179495021;179495020
Novex-1	5803	17632;17633;17634	chr2:178630295;178630294;178630293	chr2:179495022;179495021;179495020
Novex-2	5870	17833;17834;17835	chr2:178630295;178630294;178630293	chr2:179495022;179495021;179495020
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-98
• Domain position: 69
• Structural Position: 153
• Q(SASA): 0.2599
• 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
G/E	rs753855392	-1.047	0.002	N	0.405	0.285	0.112648838833	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	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
G/A	0.0944	likely_benign	0.1408	benign	-0.762	Destabilizing	0.008	N	0.233	neutral	N	0.388463802	None	None	N
G/C	0.1899	likely_benign	0.309	benign	-1.035	Destabilizing	0.984	D	0.714	prob.delet.	None	None	None	None	N
G/D	0.2888	likely_benign	0.4901	ambiguous	-1.341	Destabilizing	0.272	N	0.553	neutral	None	None	None	None	N
G/E	0.216	likely_benign	0.4034	ambiguous	-1.415	Destabilizing	0.002	N	0.405	neutral	N	0.332261029	None	None	N
G/F	0.4688	ambiguous	0.6104	pathogenic	-1.181	Destabilizing	0.724	D	0.723	deleterious	None	None	None	None	N
G/H	0.388	ambiguous	0.5835	pathogenic	-1.369	Destabilizing	0.953	D	0.637	neutral	None	None	None	None	N
G/I	0.1528	likely_benign	0.2626	benign	-0.427	Destabilizing	0.311	N	0.715	prob.delet.	None	None	None	None	N
G/K	0.4083	ambiguous	0.6492	pathogenic	-1.321	Destabilizing	0.272	N	0.629	neutral	None	None	None	None	N
G/L	0.3065	likely_benign	0.4852	ambiguous	-0.427	Destabilizing	0.272	N	0.664	prob.neutral	None	None	None	None	N
G/M	0.2949	likely_benign	0.4389	ambiguous	-0.32	Destabilizing	0.908	D	0.7	prob.delet.	None	None	None	None	N
G/N	0.2695	likely_benign	0.4228	ambiguous	-0.983	Destabilizing	0.724	D	0.524	neutral	None	None	None	None	N
G/P	0.6729	likely_pathogenic	0.7771	pathogenic	-0.498	Destabilizing	0.842	D	0.677	prob.neutral	None	None	None	None	N
G/Q	0.3119	likely_benign	0.4898	ambiguous	-1.201	Destabilizing	0.568	D	0.67	prob.neutral	None	None	None	None	N
G/R	0.2798	likely_benign	0.4904	ambiguous	-0.967	Destabilizing	0.664	D	0.666	prob.neutral	N	0.432276133	None	None	N
G/S	0.0904	likely_benign	0.129	benign	-1.222	Destabilizing	0.028	N	0.304	neutral	None	None	None	None	N
G/T	0.1131	likely_benign	0.1765	benign	-1.22	Destabilizing	0.428	N	0.61	neutral	None	None	None	None	N
G/V	0.1131	likely_benign	0.1943	benign	-0.498	Destabilizing	0.004	N	0.483	neutral	N	0.429518699	None	None	N
G/W	0.3539	ambiguous	0.4986	ambiguous	-1.51	Destabilizing	0.979	D	0.699	prob.delet.	N	0.433950163	None	None	N
G/Y	0.3897	ambiguous	0.5543	ambiguous	-1.115	Destabilizing	0.842	D	0.725	deleterious	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.