TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14326	43201;43202;43203	chr2:178633297;178633296;178633295	chr2:179498024;179498023;179498022
N2AB	12685	38278;38279;38280	chr2:178633297;178633296;178633295	chr2:179498024;179498023;179498022
N2A	11758	35497;35498;35499	chr2:178633297;178633296;178633295	chr2:179498024;179498023;179498022
N2B	5261	16006;16007;16008	chr2:178633297;178633296;178633295	chr2:179498024;179498023;179498022
Novex-1	5386	16381;16382;16383	chr2:178633297;178633296;178633295	chr2:179498024;179498023;179498022
Novex-2	5453	16582;16583;16584	chr2:178633297;178633296;178633295	chr2:179498024;179498023;179498022
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-94
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.6571
• 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
Y/C	rs1161910175	None	0.95	N	0.73	0.192	0.279370189704	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Y/C	rs1161910175	None	0.95	N	0.73	0.192	0.279370189704	gnomAD-4.0.0	2.03011E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.40999E-06	0	0
Y/H	None	None	0.623	N	0.689	0.156	0.16115917748	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

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
Y/A	0.4849	ambiguous	0.4279	ambiguous	-0.535	Destabilizing	0.236	N	0.543	neutral	None	None	None	None	N
Y/C	0.2008	likely_benign	0.1783	benign	-0.058	Destabilizing	0.95	D	0.73	deleterious	N	0.467975708	None	None	N
Y/D	0.3278	likely_benign	0.272	benign	0.612	Stabilizing	0.449	N	0.73	deleterious	N	0.412761355	None	None	N
Y/E	0.5597	ambiguous	0.5152	ambiguous	0.592	Stabilizing	0.351	N	0.543	neutral	None	None	None	None	N
Y/F	0.1436	likely_benign	0.1298	benign	-0.291	Destabilizing	0.32	N	0.641	neutral	N	0.507018286	None	None	N
Y/G	0.4232	ambiguous	0.3865	ambiguous	-0.693	Destabilizing	0.519	D	0.579	neutral	None	None	None	None	N
Y/H	0.1677	likely_benign	0.1464	benign	0.301	Stabilizing	0.623	D	0.689	prob.delet.	N	0.444625173	None	None	N
Y/I	0.5479	ambiguous	0.49	ambiguous	-0.147	Destabilizing	0.687	D	0.681	prob.neutral	None	None	None	None	N
Y/K	0.4749	ambiguous	0.4523	ambiguous	0.062	Stabilizing	0.134	N	0.533	neutral	None	None	None	None	N
Y/L	0.4456	ambiguous	0.381	ambiguous	-0.147	Destabilizing	0.236	N	0.61	neutral	None	None	None	None	N
Y/M	0.6773	likely_pathogenic	0.6292	pathogenic	-0.226	Destabilizing	0.962	D	0.627	neutral	None	None	None	None	N
Y/N	0.1988	likely_benign	0.1702	benign	-0.265	Destabilizing	0.449	N	0.735	deleterious	N	0.462978878	None	None	N
Y/P	0.7028	likely_pathogenic	0.641	pathogenic	-0.258	Destabilizing	0.687	D	0.737	deleterious	None	None	None	None	N
Y/Q	0.4189	ambiguous	0.3878	ambiguous	-0.175	Destabilizing	0.519	D	0.677	prob.neutral	None	None	None	None	N
Y/R	0.2701	likely_benign	0.2586	benign	0.245	Stabilizing	0.002	N	0.341	neutral	None	None	None	None	N
Y/S	0.2079	likely_benign	0.1813	benign	-0.578	Destabilizing	0.449	N	0.576	neutral	N	0.423654488	None	None	N
Y/T	0.4152	ambiguous	0.3764	ambiguous	-0.511	Destabilizing	0.519	D	0.665	prob.neutral	None	None	None	None	N
Y/V	0.4136	ambiguous	0.3737	ambiguous	-0.258	Destabilizing	0.519	D	0.636	neutral	None	None	None	None	N
Y/W	0.4248	ambiguous	0.4167	ambiguous	-0.474	Destabilizing	0.962	D	0.664	prob.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.