TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3309	10150;10151;10152	chr2:178764590;178764589;178764588	chr2:179629317;179629316;179629315
N2AB	3309	10150;10151;10152	chr2:178764590;178764589;178764588	chr2:179629317;179629316;179629315
N2A	3309	10150;10151;10152	chr2:178764590;178764589;178764588	chr2:179629317;179629316;179629315
N2B	3263	10012;10013;10014	chr2:178764590;178764589;178764588	chr2:179629317;179629316;179629315
Novex-1	3263	10012;10013;10014	chr2:178764590;178764589;178764588	chr2:179629317;179629316;179629315
Novex-2	3263	10012;10013;10014	chr2:178764590;178764589;178764588	chr2:179629317;179629316;179629315
Novex-3	3309	10150;10151;10152	chr2:178764590;178764589;178764588	chr2:179629317;179629316;179629315

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-23
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.1339
• 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
Y/H	rs2090020782	None	1.0	D	0.794	0.917	0.850723522503	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.06954E-04	0
Y/H	rs2090020782	None	1.0	D	0.794	0.917	0.850723522503	gnomAD-4.0.0	6.56961E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.06954E-04	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
Y/A	0.9978	likely_pathogenic	0.9968	pathogenic	-2.269	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
Y/C	0.9634	likely_pathogenic	0.9495	pathogenic	-1.465	Destabilizing	1.0	D	0.875	deleterious	D	0.781871977	None	None	N
Y/D	0.9989	likely_pathogenic	0.9985	pathogenic	-2.991	Highly Destabilizing	1.0	D	0.89	deleterious	D	0.781973364	None	None	N
Y/E	0.9994	likely_pathogenic	0.9993	pathogenic	-2.74	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/F	0.2943	likely_benign	0.2614	benign	-0.738	Destabilizing	0.999	D	0.707	prob.neutral	D	0.608253164	None	None	N
Y/G	0.9961	likely_pathogenic	0.9944	pathogenic	-2.726	Highly Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
Y/H	0.9902	likely_pathogenic	0.9841	pathogenic	-2.035	Highly Destabilizing	1.0	D	0.794	deleterious	D	0.782077687	None	None	N
Y/I	0.9484	likely_pathogenic	0.935	pathogenic	-0.755	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
Y/K	0.9994	likely_pathogenic	0.999	pathogenic	-1.846	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
Y/L	0.8666	likely_pathogenic	0.858	pathogenic	-0.755	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
Y/M	0.9861	likely_pathogenic	0.9807	pathogenic	-0.775	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
Y/N	0.9935	likely_pathogenic	0.99	pathogenic	-2.801	Highly Destabilizing	1.0	D	0.887	deleterious	D	0.781871977	None	None	N
Y/P	0.9988	likely_pathogenic	0.9982	pathogenic	-1.275	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
Y/Q	0.9994	likely_pathogenic	0.999	pathogenic	-2.346	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
Y/R	0.9972	likely_pathogenic	0.9958	pathogenic	-2.127	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/S	0.9947	likely_pathogenic	0.9918	pathogenic	-3.087	Highly Destabilizing	1.0	D	0.889	deleterious	D	0.781871977	None	None	N
Y/T	0.9977	likely_pathogenic	0.9963	pathogenic	-2.686	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/V	0.9177	likely_pathogenic	0.9041	pathogenic	-1.275	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
Y/W	0.9132	likely_pathogenic	0.8831	pathogenic	-0.113	Destabilizing	1.0	D	0.792	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.