TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31596	95011;95012;95013	chr2:178546642;178546641;178546640	chr2:179411369;179411368;179411367
N2AB	29955	90088;90089;90090	chr2:178546642;178546641;178546640	chr2:179411369;179411368;179411367
N2A	29028	87307;87308;87309	chr2:178546642;178546641;178546640	chr2:179411369;179411368;179411367
N2B	22531	67816;67817;67818	chr2:178546642;178546641;178546640	chr2:179411369;179411368;179411367
Novex-1	22656	68191;68192;68193	chr2:178546642;178546641;178546640	chr2:179411369;179411368;179411367
Novex-2	22723	68392;68393;68394	chr2:178546642;178546641;178546640	chr2:179411369;179411368;179411367
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Fn3-118
• Domain position: 91
• Structural Position: 120
• Q(SASA): 0.283
• 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/A	None	None	0.103	N	0.385	0.171	0.149567049428	gnomAD-4.0.0	6.84407E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99711E-07	0	0
G/E	None	None	0.968	N	0.586	0.327	0.338592109245	gnomAD-4.0.0	1.36881E-06	None	None	None	None	I	None	0	0	None	0	2.52156E-05	None	0	0	8.99711E-07	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
G/A	0.0886	likely_benign	0.0778	benign	-0.695	Destabilizing	0.103	N	0.385	neutral	N	0.312800495	None	None	I
G/C	0.2724	likely_benign	0.2191	benign	-1.004	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	I
G/D	0.6228	likely_pathogenic	0.5267	ambiguous	-0.781	Destabilizing	0.988	D	0.575	neutral	None	None	None	None	I
G/E	0.5002	ambiguous	0.4026	ambiguous	-0.917	Destabilizing	0.968	D	0.586	neutral	N	0.380870927	None	None	I
G/F	0.7834	likely_pathogenic	0.7403	pathogenic	-1.219	Destabilizing	0.996	D	0.771	deleterious	None	None	None	None	I
G/H	0.7296	likely_pathogenic	0.6555	pathogenic	-0.97	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	I
G/I	0.4629	ambiguous	0.3563	ambiguous	-0.653	Destabilizing	0.988	D	0.755	deleterious	None	None	None	None	I
G/K	0.8658	likely_pathogenic	0.7786	pathogenic	-1.077	Destabilizing	0.976	D	0.593	neutral	None	None	None	None	I
G/L	0.6693	likely_pathogenic	0.5685	pathogenic	-0.653	Destabilizing	0.976	D	0.665	neutral	None	None	None	None	I
G/M	0.7177	likely_pathogenic	0.6231	pathogenic	-0.564	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	I
G/N	0.6269	likely_pathogenic	0.5209	ambiguous	-0.696	Destabilizing	0.996	D	0.491	neutral	None	None	None	None	I
G/P	0.2285	likely_benign	0.2051	benign	-0.631	Destabilizing	0.015	N	0.444	neutral	None	None	None	None	I
G/Q	0.6853	likely_pathogenic	0.5805	pathogenic	-0.996	Destabilizing	0.996	D	0.687	prob.neutral	None	None	None	None	I
G/R	0.7711	likely_pathogenic	0.6703	pathogenic	-0.644	Destabilizing	0.984	D	0.686	prob.neutral	N	0.385084668	None	None	I
G/S	0.139	likely_benign	0.114	benign	-0.923	Destabilizing	0.851	D	0.444	neutral	None	None	None	None	I
G/T	0.3126	likely_benign	0.2391	benign	-0.99	Destabilizing	0.976	D	0.572	neutral	None	None	None	None	I
G/V	0.2978	likely_benign	0.22	benign	-0.631	Destabilizing	0.968	D	0.651	neutral	N	0.389759769	None	None	I
G/W	0.6279	likely_pathogenic	0.6066	pathogenic	-1.361	Destabilizing	0.999	D	0.679	prob.neutral	N	0.416101009	None	None	I
G/Y	0.5937	likely_pathogenic	0.5464	ambiguous	-1.033	Destabilizing	0.999	D	0.771	deleterious	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.