TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13993	42202;42203;42204	chr2:178635212;178635211;178635210	chr2:179499939;179499938;179499937
N2AB	12352	37279;37280;37281	chr2:178635212;178635211;178635210	chr2:179499939;179499938;179499937
N2A	11425	34498;34499;34500	chr2:178635212;178635211;178635210	chr2:179499939;179499938;179499937
N2B	4928	15007;15008;15009	chr2:178635212;178635211;178635210	chr2:179499939;179499938;179499937
Novex-1	5053	15382;15383;15384	chr2:178635212;178635211;178635210	chr2:179499939;179499938;179499937
Novex-2	5120	15583;15584;15585	chr2:178635212;178635211;178635210	chr2:179499939;179499938;179499937
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-90
• Domain position: 29
• Structural Position: 44
• Q(SASA): 0.2593
• 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
I/V	rs978359923	None	None	N	0.154	0.086	0.117506650769	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
I/A	0.882	likely_pathogenic	0.8002	pathogenic	-1.353	Destabilizing	0.034	N	0.471	neutral	None	None	None	None	N
I/C	0.9266	likely_pathogenic	0.8973	pathogenic	-0.869	Destabilizing	0.823	D	0.629	neutral	None	None	None	None	N
I/D	0.9848	likely_pathogenic	0.9743	pathogenic	-0.888	Destabilizing	0.552	D	0.762	deleterious	None	None	None	None	N
I/E	0.9571	likely_pathogenic	0.9292	pathogenic	-0.901	Destabilizing	0.552	D	0.701	prob.delet.	None	None	None	None	N
I/F	0.6046	likely_pathogenic	0.4855	ambiguous	-0.958	Destabilizing	0.314	N	0.539	neutral	N	0.454047766	None	None	N
I/G	0.9811	likely_pathogenic	0.9616	pathogenic	-1.642	Destabilizing	0.552	D	0.619	neutral	None	None	None	None	N
I/H	0.9608	likely_pathogenic	0.9295	pathogenic	-0.792	Destabilizing	0.934	D	0.769	deleterious	None	None	None	None	N
I/K	0.9512	likely_pathogenic	0.9135	pathogenic	-0.962	Destabilizing	0.552	D	0.701	prob.delet.	None	None	None	None	N
I/L	0.3734	ambiguous	0.2788	benign	-0.648	Destabilizing	0.012	N	0.279	neutral	N	0.422052624	None	None	N
I/M	0.4368	ambiguous	0.311	benign	-0.592	Destabilizing	0.314	N	0.552	neutral	N	0.454293924	None	None	N
I/N	0.8691	likely_pathogenic	0.7721	pathogenic	-0.791	Destabilizing	0.739	D	0.769	deleterious	N	0.45518166	None	None	N
I/P	0.9827	likely_pathogenic	0.9797	pathogenic	-0.851	Destabilizing	0.789	D	0.759	deleterious	None	None	None	None	N
I/Q	0.9486	likely_pathogenic	0.9029	pathogenic	-0.96	Destabilizing	0.789	D	0.786	deleterious	None	None	None	None	N
I/R	0.9341	likely_pathogenic	0.8895	pathogenic	-0.36	Destabilizing	0.552	D	0.775	deleterious	None	None	None	None	N
I/S	0.8794	likely_pathogenic	0.7832	pathogenic	-1.329	Destabilizing	0.314	N	0.59	neutral	N	0.453458516	None	None	N
I/T	0.7112	likely_pathogenic	0.5807	pathogenic	-1.22	Destabilizing	0.061	N	0.537	neutral	N	0.424970439	None	None	N
I/V	0.09	likely_benign	0.0825	benign	-0.851	Destabilizing	None	N	0.154	neutral	N	0.411711599	None	None	N
I/W	0.9884	likely_pathogenic	0.9792	pathogenic	-1.011	Destabilizing	0.934	D	0.765	deleterious	None	None	None	None	N
I/Y	0.9124	likely_pathogenic	0.8577	pathogenic	-0.789	Destabilizing	0.552	D	0.631	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.