TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29679	89260;89261;89262	chr2:178554076;178554075;178554074	chr2:179418803;179418802;179418801
N2AB	28038	84337;84338;84339	chr2:178554076;178554075;178554074	chr2:179418803;179418802;179418801
N2A	27111	81556;81557;81558	chr2:178554076;178554075;178554074	chr2:179418803;179418802;179418801
N2B	20614	62065;62066;62067	chr2:178554076;178554075;178554074	chr2:179418803;179418802;179418801
Novex-1	20739	62440;62441;62442	chr2:178554076;178554075;178554074	chr2:179418803;179418802;179418801
Novex-2	20806	62641;62642;62643	chr2:178554076;178554075;178554074	chr2:179418803;179418802;179418801
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-104
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.3021
• Predicted PPI site: I

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
G/R	rs774651157	0.011	None	N	0.192	0.172	0.299427821978	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	5.56E-05	None	0	None	0	0	0
G/R	rs774651157	0.011	None	N	0.192	0.172	0.299427821978	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
G/R	rs774651157	0.011	None	N	0.192	0.172	0.299427821978	gnomAD-4.0.0	2.66471E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.55994E-05	0	1.60102E-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
G/A	0.0813	likely_benign	0.091	benign	-0.288	Destabilizing	None	N	0.177	neutral	N	0.447754854	None	None	I
G/C	0.1508	likely_benign	0.1602	benign	-0.57	Destabilizing	0.676	D	0.462	neutral	None	None	None	None	I
G/D	0.3895	ambiguous	0.4968	ambiguous	0.087	Stabilizing	0.072	N	0.407	neutral	None	None	None	None	I
G/E	0.308	likely_benign	0.4084	ambiguous	0.015	Stabilizing	0.012	N	0.429	neutral	N	0.405713443	None	None	I
G/F	0.4606	ambiguous	0.5483	ambiguous	-0.648	Destabilizing	0.356	N	0.466	neutral	None	None	None	None	I
G/H	0.337	likely_benign	0.3872	ambiguous	-0.512	Destabilizing	0.356	N	0.446	neutral	None	None	None	None	I
G/I	0.1736	likely_benign	0.2092	benign	-0.086	Destabilizing	0.214	N	0.46	neutral	None	None	None	None	I
G/K	0.447	ambiguous	0.5374	ambiguous	-0.536	Destabilizing	0.016	N	0.437	neutral	None	None	None	None	I
G/L	0.2508	likely_benign	0.3075	benign	-0.086	Destabilizing	0.038	N	0.429	neutral	None	None	None	None	I
G/M	0.3157	likely_benign	0.3537	ambiguous	-0.336	Destabilizing	0.356	N	0.471	neutral	None	None	None	None	I
G/N	0.2447	likely_benign	0.2865	benign	-0.256	Destabilizing	0.072	N	0.457	neutral	None	None	None	None	I
G/P	0.8112	likely_pathogenic	0.8557	pathogenic	-0.115	Destabilizing	0.072	N	0.417	neutral	None	None	None	None	I
G/Q	0.3038	likely_benign	0.3427	ambiguous	-0.378	Destabilizing	0.003	N	0.219	neutral	None	None	None	None	I
G/R	0.3177	likely_benign	0.3886	ambiguous	-0.296	Destabilizing	None	N	0.192	neutral	N	0.340280672	None	None	I
G/S	0.0875	likely_benign	0.0954	benign	-0.573	Destabilizing	0.001	N	0.195	neutral	None	None	None	None	I
G/T	0.1094	likely_benign	0.1201	benign	-0.544	Destabilizing	0.038	N	0.422	neutral	None	None	None	None	I
G/V	0.1117	likely_benign	0.1357	benign	-0.115	Destabilizing	0.029	N	0.421	neutral	N	0.447274851	None	None	I
G/W	0.4053	ambiguous	0.4631	ambiguous	-0.924	Destabilizing	0.864	D	0.454	neutral	None	None	None	None	I
G/Y	0.3436	ambiguous	0.415	ambiguous	-0.489	Destabilizing	0.356	N	0.469	neutral	None	None	None	None	I

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.