TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31960	96103;96104;96105	chr2:178544351;178544350;178544349	chr2:179409078;179409077;179409076
N2AB	30319	91180;91181;91182	chr2:178544351;178544350;178544349	chr2:179409078;179409077;179409076
N2A	29392	88399;88400;88401	chr2:178544351;178544350;178544349	chr2:179409078;179409077;179409076
N2B	22895	68908;68909;68910	chr2:178544351;178544350;178544349	chr2:179409078;179409077;179409076
Novex-1	23020	69283;69284;69285	chr2:178544351;178544350;178544349	chr2:179409078;179409077;179409076
Novex-2	23087	69484;69485;69486	chr2:178544351;178544350;178544349	chr2:179409078;179409077;179409076
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-121
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.083
• 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
H/R	rs776521449	-1.057	0.997	N	0.663	0.361	0.331365685468	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
H/R	rs776521449	-1.057	0.997	N	0.663	0.361	0.331365685468	gnomAD-4.0.0	4.77406E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71716E-06	0	3.02425E-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
H/A	0.7358	likely_pathogenic	0.6933	pathogenic	-1.475	Destabilizing	0.997	D	0.658	neutral	None	None	None	None	N
H/C	0.3802	ambiguous	0.3579	ambiguous	-0.873	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
H/D	0.6175	likely_pathogenic	0.5338	ambiguous	-1.031	Destabilizing	0.997	D	0.667	neutral	N	0.425029923	None	None	N
H/E	0.8208	likely_pathogenic	0.7836	pathogenic	-0.862	Destabilizing	0.997	D	0.607	neutral	None	None	None	None	N
H/F	0.6645	likely_pathogenic	0.6446	pathogenic	0.099	Stabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
H/G	0.6736	likely_pathogenic	0.649	pathogenic	-1.9	Destabilizing	0.997	D	0.677	prob.neutral	None	None	None	None	N
H/I	0.7318	likely_pathogenic	0.6983	pathogenic	-0.251	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
H/K	0.8745	likely_pathogenic	0.8362	pathogenic	-1.007	Destabilizing	0.997	D	0.667	neutral	None	None	None	None	N
H/L	0.4466	ambiguous	0.3959	ambiguous	-0.251	Destabilizing	0.999	D	0.72	prob.delet.	N	0.435785634	None	None	N
H/M	0.7699	likely_pathogenic	0.7578	pathogenic	-0.544	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
H/N	0.1654	likely_benign	0.164	benign	-1.48	Destabilizing	0.997	D	0.597	neutral	N	0.334026704	None	None	N
H/P	0.5076	ambiguous	0.4208	ambiguous	-0.644	Destabilizing	0.999	D	0.709	prob.delet.	N	0.445559911	None	None	N
H/Q	0.6607	likely_pathogenic	0.6184	pathogenic	-1.132	Destabilizing	0.999	D	0.687	prob.neutral	N	0.45695034	None	None	N
H/R	0.7428	likely_pathogenic	0.6684	pathogenic	-1.281	Destabilizing	0.997	D	0.663	neutral	N	0.448504216	None	None	N
H/S	0.443	ambiguous	0.4353	ambiguous	-1.685	Destabilizing	0.997	D	0.676	prob.neutral	None	None	None	None	N
H/T	0.5745	likely_pathogenic	0.5515	ambiguous	-1.387	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
H/V	0.6845	likely_pathogenic	0.6419	pathogenic	-0.644	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
H/W	0.7878	likely_pathogenic	0.759	pathogenic	0.659	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
H/Y	0.3621	ambiguous	0.3071	benign	0.594	Stabilizing	0.997	D	0.603	neutral	N	0.393267008	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.