TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31808	95647;95648;95649	chr2:178545688;178545687;178545686	chr2:179410415;179410414;179410413
N2AB	30167	90724;90725;90726	chr2:178545688;178545687;178545686	chr2:179410415;179410414;179410413
N2A	29240	87943;87944;87945	chr2:178545688;178545687;178545686	chr2:179410415;179410414;179410413
N2B	22743	68452;68453;68454	chr2:178545688;178545687;178545686	chr2:179410415;179410414;179410413
Novex-1	22868	68827;68828;68829	chr2:178545688;178545687;178545686	chr2:179410415;179410414;179410413
Novex-2	22935	69028;69029;69030	chr2:178545688;178545687;178545686	chr2:179410415;179410414;179410413
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-120
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.4964
• 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
P/Q	None	None	1.0	D	0.753	0.726	0.763425995813	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-06	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
P/A	0.586	likely_pathogenic	0.6017	pathogenic	-1.583	Destabilizing	0.603	D	0.341	neutral	D	0.63073552	None	None	N
P/C	0.9681	likely_pathogenic	0.968	pathogenic	-2.009	Highly Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
P/D	0.9994	likely_pathogenic	0.9993	pathogenic	-2.955	Highly Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
P/E	0.9982	likely_pathogenic	0.998	pathogenic	-2.91	Highly Destabilizing	0.999	D	0.739	deleterious	None	None	None	None	N
P/F	0.999	likely_pathogenic	0.9989	pathogenic	-1.318	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
P/G	0.9833	likely_pathogenic	0.9827	pathogenic	-1.892	Destabilizing	0.993	D	0.739	deleterious	None	None	None	None	N
P/H	0.9967	likely_pathogenic	0.9962	pathogenic	-1.305	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
P/I	0.9868	likely_pathogenic	0.9847	pathogenic	-0.801	Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
P/K	0.9991	likely_pathogenic	0.9989	pathogenic	-1.463	Destabilizing	0.999	D	0.737	deleterious	None	None	None	None	N
P/L	0.946	likely_pathogenic	0.9441	pathogenic	-0.801	Destabilizing	0.997	D	0.737	deleterious	D	0.672696601	None	None	N
P/M	0.9932	likely_pathogenic	0.9932	pathogenic	-0.995	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
P/N	0.9984	likely_pathogenic	0.9984	pathogenic	-1.69	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
P/Q	0.9946	likely_pathogenic	0.9939	pathogenic	-1.898	Destabilizing	1.0	D	0.753	deleterious	D	0.672898405	None	None	N
P/R	0.9956	likely_pathogenic	0.9949	pathogenic	-0.956	Destabilizing	0.999	D	0.846	deleterious	D	0.672696601	None	None	N
P/S	0.9236	likely_pathogenic	0.9267	pathogenic	-2.088	Highly Destabilizing	0.995	D	0.742	deleterious	D	0.624204549	None	None	N
P/T	0.9464	likely_pathogenic	0.9452	pathogenic	-1.939	Destabilizing	0.997	D	0.722	deleterious	D	0.672696601	None	None	N
P/V	0.9573	likely_pathogenic	0.9499	pathogenic	-1.033	Destabilizing	0.998	D	0.737	deleterious	None	None	None	None	N
P/W	0.9998	likely_pathogenic	0.9997	pathogenic	-1.571	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
P/Y	0.9994	likely_pathogenic	0.9993	pathogenic	-1.222	Destabilizing	1.0	D	0.829	deleterious	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.