TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20033	60322;60323;60324	chr2:178591722;178591721;178591720	chr2:179456449;179456448;179456447
N2AB	18392	55399;55400;55401	chr2:178591722;178591721;178591720	chr2:179456449;179456448;179456447
N2A	17465	52618;52619;52620	chr2:178591722;178591721;178591720	chr2:179456449;179456448;179456447
N2B	10968	33127;33128;33129	chr2:178591722;178591721;178591720	chr2:179456449;179456448;179456447
Novex-1	11093	33502;33503;33504	chr2:178591722;178591721;178591720	chr2:179456449;179456448;179456447
Novex-2	11160	33703;33704;33705	chr2:178591722;178591721;178591720	chr2:179456449;179456448;179456447
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Fn3-33
• Domain position: 57
• Structural Position: 89
• Q(SASA): 0.2662
• 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
L/V	rs878993043	-0.923	0.946	N	0.428	0.123	None	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
L/V	rs878993043	-0.923	0.946	N	0.428	0.123	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	5.89E-05	0	0
L/V	rs878993043	-0.923	0.946	N	0.428	0.123	None	gnomAD-4.0.0	1.02556E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.67605E-05	0	2.84495E-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
L/A	0.2354	likely_benign	0.26	benign	-1.957	Destabilizing	0.825	D	0.463	neutral	None	None	None	None	N
L/C	0.3873	ambiguous	0.4274	ambiguous	-1.056	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
L/D	0.6835	likely_pathogenic	0.7469	pathogenic	-2.129	Highly Destabilizing	0.988	D	0.661	neutral	None	None	None	None	N
L/E	0.3418	ambiguous	0.3905	ambiguous	-1.959	Destabilizing	0.976	D	0.643	neutral	None	None	None	None	N
L/F	0.2925	likely_benign	0.3084	benign	-1.18	Destabilizing	0.995	D	0.52	neutral	N	0.492545781	None	None	N
L/G	0.4616	ambiguous	0.5056	ambiguous	-2.421	Highly Destabilizing	0.976	D	0.643	neutral	None	None	None	None	N
L/H	0.3026	likely_benign	0.3301	benign	-1.756	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
L/I	0.1708	likely_benign	0.1852	benign	-0.657	Destabilizing	0.946	D	0.403	neutral	N	0.473439945	None	None	N
L/K	0.2208	likely_benign	0.2418	benign	-1.456	Destabilizing	0.976	D	0.614	neutral	None	None	None	None	N
L/M	0.1046	likely_benign	0.1107	benign	-0.476	Destabilizing	0.996	D	0.547	neutral	None	None	None	None	N
L/N	0.2951	likely_benign	0.3467	ambiguous	-1.678	Destabilizing	0.988	D	0.685	prob.neutral	None	None	None	None	N
L/P	0.1635	likely_benign	0.2119	benign	-1.068	Destabilizing	0.005	N	0.517	neutral	None	None	None	None	N
L/Q	0.1566	likely_benign	0.1669	benign	-1.64	Destabilizing	0.988	D	0.648	neutral	None	None	None	None	N
L/R	0.1743	likely_benign	0.1815	benign	-1.077	Destabilizing	0.988	D	0.649	neutral	None	None	None	None	N
L/S	0.2787	likely_benign	0.3223	benign	-2.292	Highly Destabilizing	0.896	D	0.593	neutral	N	0.45535283	None	None	N
L/T	0.1048	likely_benign	0.1194	benign	-1.99	Destabilizing	0.919	D	0.525	neutral	None	None	None	None	N
L/V	0.1257	likely_benign	0.1346	benign	-1.068	Destabilizing	0.946	D	0.428	neutral	N	0.464569746	None	None	N
L/W	0.4039	ambiguous	0.4284	ambiguous	-1.527	Destabilizing	0.999	D	0.675	neutral	None	None	None	None	N
L/Y	0.4759	ambiguous	0.504	ambiguous	-1.174	Destabilizing	0.996	D	0.623	neutral	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.