TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35186	105781;105782;105783	chr2:178531059;178531058;178531057	chr2:179395786;179395785;179395784
N2AB	33545	100858;100859;100860	chr2:178531059;178531058;178531057	chr2:179395786;179395785;179395784
N2A	32618	98077;98078;98079	chr2:178531059;178531058;178531057	chr2:179395786;179395785;179395784
N2B	26121	78586;78587;78588	chr2:178531059;178531058;178531057	chr2:179395786;179395785;179395784
Novex-1	26246	78961;78962;78963	chr2:178531059;178531058;178531057	chr2:179395786;179395785;179395784
Novex-2	26313	79162;79163;79164	chr2:178531059;178531058;178531057	chr2:179395786;179395785;179395784
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-164
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0484
• 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
F/S	rs758159045	-2.957	0.739	N	0.819	0.516	0.502939388887	gnomAD-2.1.1	1.2E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.8E-05	None	0	0	0
F/S	rs758159045	-2.957	0.739	N	0.819	0.516	0.502939388887	gnomAD-4.0.0	6.84138E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49696E-06	5.79656E-05	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
F/A	0.9488	likely_pathogenic	0.9556	pathogenic	-1.92	Destabilizing	0.345	N	0.785	deleterious	None	None	None	None	N
F/C	0.8274	likely_pathogenic	0.8429	pathogenic	-0.967	Destabilizing	0.97	D	0.852	deleterious	N	0.488279773	None	None	N
F/D	0.9991	likely_pathogenic	0.9992	pathogenic	-2.8	Highly Destabilizing	0.919	D	0.869	deleterious	None	None	None	None	N
F/E	0.998	likely_pathogenic	0.9982	pathogenic	-2.588	Highly Destabilizing	0.789	D	0.857	deleterious	None	None	None	None	N
F/G	0.9903	likely_pathogenic	0.9918	pathogenic	-2.303	Highly Destabilizing	0.789	D	0.835	deleterious	None	None	None	None	N
F/H	0.9878	likely_pathogenic	0.9886	pathogenic	-2.105	Highly Destabilizing	0.977	D	0.787	deleterious	None	None	None	None	N
F/I	0.5207	ambiguous	0.5326	ambiguous	-0.653	Destabilizing	0.166	N	0.643	neutral	N	0.481584134	None	None	N
F/K	0.9977	likely_pathogenic	0.9978	pathogenic	-1.75	Destabilizing	0.789	D	0.849	deleterious	None	None	None	None	N
F/L	0.7869	likely_pathogenic	0.7996	pathogenic	-0.653	Destabilizing	0.001	N	0.355	neutral	N	0.329440297	None	None	N
F/M	0.6931	likely_pathogenic	0.7057	pathogenic	-0.639	Destabilizing	0.045	N	0.493	neutral	None	None	None	None	N
F/N	0.9967	likely_pathogenic	0.9971	pathogenic	-2.437	Highly Destabilizing	0.919	D	0.869	deleterious	None	None	None	None	N
F/P	0.9996	likely_pathogenic	0.9997	pathogenic	-1.089	Destabilizing	0.919	D	0.87	deleterious	None	None	None	None	N
F/Q	0.9954	likely_pathogenic	0.9956	pathogenic	-2.104	Highly Destabilizing	0.789	D	0.871	deleterious	None	None	None	None	N
F/R	0.9917	likely_pathogenic	0.9918	pathogenic	-2.013	Highly Destabilizing	0.789	D	0.869	deleterious	None	None	None	None	N
F/S	0.9839	likely_pathogenic	0.9861	pathogenic	-2.614	Highly Destabilizing	0.739	D	0.819	deleterious	N	0.488533263	None	None	N
F/T	0.976	likely_pathogenic	0.9784	pathogenic	-2.287	Highly Destabilizing	0.649	D	0.811	deleterious	None	None	None	None	N
F/V	0.5288	ambiguous	0.5433	ambiguous	-1.089	Destabilizing	0.076	N	0.728	prob.delet.	N	0.491878486	None	None	N
F/W	0.8189	likely_pathogenic	0.8269	pathogenic	-0.449	Destabilizing	0.977	D	0.659	neutral	None	None	None	None	N
F/Y	0.5908	likely_pathogenic	0.6009	pathogenic	-0.812	Destabilizing	0.446	N	0.631	neutral	N	0.469922029	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.