TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6405	19438;19439;19440	chr2:178728713;178728712;178728711	chr2:179593440;179593439;179593438
N2AB	6088	18487;18488;18489	chr2:178728713;178728712;178728711	chr2:179593440;179593439;179593438
N2A	5161	15706;15707;15708	chr2:178728713;178728712;178728711	chr2:179593440;179593439;179593438
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-48
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.5421
• 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/Q	rs1431926097	-0.07	0.998	N	0.642	0.318	0.441636318388	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
E/Q	rs1431926097	-0.07	0.998	N	0.642	0.318	0.441636318388	gnomAD-4.0.0	1.59412E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86541E-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
E/A	0.3149	likely_benign	0.2962	benign	-0.753	Destabilizing	0.994	D	0.607	neutral	N	0.510446537	None	None	N
E/C	0.9526	likely_pathogenic	0.9418	pathogenic	-0.221	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
E/D	0.3738	ambiguous	0.3257	benign	-0.926	Destabilizing	0.104	N	0.256	neutral	D	0.53134739	None	None	N
E/F	0.9164	likely_pathogenic	0.897	pathogenic	-0.493	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
E/G	0.4948	ambiguous	0.437	ambiguous	-1.056	Destabilizing	0.994	D	0.624	neutral	D	0.53171757	None	None	N
E/H	0.6719	likely_pathogenic	0.648	pathogenic	-0.672	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	N
E/I	0.6442	likely_pathogenic	0.5895	pathogenic	0.053	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
E/K	0.3305	likely_benign	0.3058	benign	-0.22	Destabilizing	0.994	D	0.551	neutral	N	0.493632502	None	None	N
E/L	0.6915	likely_pathogenic	0.648	pathogenic	0.053	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
E/M	0.719	likely_pathogenic	0.6859	pathogenic	0.481	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/N	0.5533	ambiguous	0.4936	ambiguous	-0.635	Destabilizing	0.998	D	0.651	neutral	None	None	None	None	N
E/P	0.9494	likely_pathogenic	0.9635	pathogenic	-0.194	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/Q	0.1633	likely_benign	0.1592	benign	-0.561	Destabilizing	0.998	D	0.642	neutral	N	0.512953631	None	None	N
E/R	0.4501	ambiguous	0.4469	ambiguous	-0.028	Destabilizing	0.999	D	0.675	neutral	None	None	None	None	N
E/S	0.3782	ambiguous	0.3417	ambiguous	-0.875	Destabilizing	0.992	D	0.553	neutral	None	None	None	None	N
E/T	0.3673	ambiguous	0.3264	benign	-0.625	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
E/V	0.3946	ambiguous	0.3606	ambiguous	-0.194	Destabilizing	0.999	D	0.727	prob.delet.	N	0.505473014	None	None	N
E/W	0.9691	likely_pathogenic	0.9665	pathogenic	-0.288	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
E/Y	0.8538	likely_pathogenic	0.832	pathogenic	-0.239	Destabilizing	1.0	D	0.743	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.