TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15436	46531;46532;46533	chr2:178620111;178620110;178620109	chr2:179484838;179484837;179484836
N2AB	13795	41608;41609;41610	chr2:178620111;178620110;178620109	chr2:179484838;179484837;179484836
N2A	12868	38827;38828;38829	chr2:178620111;178620110;178620109	chr2:179484838;179484837;179484836
N2B	6371	19336;19337;19338	chr2:178620111;178620110;178620109	chr2:179484838;179484837;179484836
Novex-1	6496	19711;19712;19713	chr2:178620111;178620110;178620109	chr2:179484838;179484837;179484836
Novex-2	6563	19912;19913;19914	chr2:178620111;178620110;178620109	chr2:179484838;179484837;179484836
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-106
• Domain position: 46
• Structural Position: 121
• Q(SASA): 0.1432
• 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	None	None	1.0	D	0.793	0.696	0.603487413129	gnomAD-4.0.0	1.60326E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.46417E-05	0
Y/H	rs748548136	-1.625	1.0	D	0.734	0.556	0.441844919209	gnomAD-2.1.1	4.09E-06	None	None	None	None	N	None	6.5E-05	0	None	0	0	None	0	None	0	0	0
Y/H	rs748548136	-1.625	1.0	D	0.734	0.556	0.441844919209	gnomAD-3.1.2	1.98E-05	None	None	None	None	N	None	4.83E-05	6.57E-05	0	0	0	None	0	0	0	0	0
Y/H	rs748548136	-1.625	1.0	D	0.734	0.556	0.441844919209	gnomAD-4.0.0	5.59456E-06	None	None	None	None	N	None	1.07173E-04	1.68731E-05	None	0	0	None	0	0	0	0	0
Y/N	rs748548136	-2.744	1.0	D	0.825	0.673	0.718952573792	gnomAD-2.1.1	4.09E-06	None	None	None	None	N	None	0	2.96E-05	None	0	0	None	0	None	0	0	0
Y/N	rs748548136	-2.744	1.0	D	0.825	0.673	0.718952573792	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.57E-05	0	0	0	None	0	0	0	0	0
Y/N	rs748548136	-2.744	1.0	D	0.825	0.673	0.718952573792	gnomAD-4.0.0	3.10809E-06	None	None	None	None	N	None	0	5.06192E-05	None	0	0	None	0	0	0	0	3.21213E-05

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	0.9684	likely_pathogenic	0.9773	pathogenic	-2.77	Highly Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
Y/C	0.6438	likely_pathogenic	0.6539	pathogenic	-1.944	Destabilizing	1.0	D	0.793	deleterious	D	0.679615735	None	None	N
Y/D	0.9628	likely_pathogenic	0.9788	pathogenic	-3.124	Highly Destabilizing	1.0	D	0.839	deleterious	D	0.718300733	None	None	N
Y/E	0.9801	likely_pathogenic	0.9869	pathogenic	-2.901	Highly Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
Y/F	0.2009	likely_benign	0.2339	benign	-0.956	Destabilizing	0.999	D	0.521	neutral	N	0.504783193	None	None	N
Y/G	0.9518	likely_pathogenic	0.9581	pathogenic	-3.21	Highly Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
Y/H	0.6748	likely_pathogenic	0.7317	pathogenic	-1.943	Destabilizing	1.0	D	0.734	prob.delet.	D	0.535731519	None	None	N
Y/I	0.8564	likely_pathogenic	0.8811	pathogenic	-1.322	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
Y/K	0.9861	likely_pathogenic	0.9891	pathogenic	-2.39	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
Y/L	0.8199	likely_pathogenic	0.852	pathogenic	-1.322	Destabilizing	0.999	D	0.655	neutral	None	None	None	None	N
Y/M	0.8939	likely_pathogenic	0.9229	pathogenic	-1.177	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
Y/N	0.7633	likely_pathogenic	0.8451	pathogenic	-3.272	Highly Destabilizing	1.0	D	0.825	deleterious	D	0.717943892	None	None	N
Y/P	0.9953	likely_pathogenic	0.9967	pathogenic	-1.818	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Y/Q	0.9647	likely_pathogenic	0.978	pathogenic	-2.914	Highly Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
Y/R	0.9626	likely_pathogenic	0.9723	pathogenic	-2.322	Highly Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
Y/S	0.9192	likely_pathogenic	0.946	pathogenic	-3.634	Highly Destabilizing	1.0	D	0.795	deleterious	D	0.655130454	None	None	N
Y/T	0.9487	likely_pathogenic	0.9667	pathogenic	-3.278	Highly Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
Y/V	0.7841	likely_pathogenic	0.8202	pathogenic	-1.818	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
Y/W	0.6717	likely_pathogenic	0.7371	pathogenic	-0.317	Destabilizing	1.0	D	0.725	prob.delet.	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.