TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29115	87568;87569;87570	chr2:178558011;178558010;178558009	chr2:179422738;179422737;179422736
N2AB	27474	82645;82646;82647	chr2:178558011;178558010;178558009	chr2:179422738;179422737;179422736
N2A	26547	79864;79865;79866	chr2:178558011;178558010;178558009	chr2:179422738;179422737;179422736
N2B	20050	60373;60374;60375	chr2:178558011;178558010;178558009	chr2:179422738;179422737;179422736
Novex-1	20175	60748;60749;60750	chr2:178558011;178558010;178558009	chr2:179422738;179422737;179422736
Novex-2	20242	60949;60950;60951	chr2:178558011;178558010;178558009	chr2:179422738;179422737;179422736
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-145
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.1326
• 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/D	None	None	1.0	D	0.867	0.815	0.904560257206	gnomAD-4.0.0	6.84212E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99433E-07	0	0
Y/H	rs1181280302	-2.249	1.0	D	0.797	0.839	0.734356017273	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
Y/H	rs1181280302	-2.249	1.0	D	0.797	0.839	0.734356017273	gnomAD-4.0.0	5.47369E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.19546E-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
Y/A	0.9933	likely_pathogenic	0.9932	pathogenic	-2.645	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
Y/C	0.8584	likely_pathogenic	0.8497	pathogenic	-1.949	Destabilizing	1.0	D	0.815	deleterious	D	0.570540615	None	None	N
Y/D	0.9959	likely_pathogenic	0.9962	pathogenic	-2.738	Highly Destabilizing	1.0	D	0.867	deleterious	D	0.596078727	None	None	N
Y/E	0.9981	likely_pathogenic	0.998	pathogenic	-2.497	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
Y/F	0.2184	likely_benign	0.1968	benign	-0.878	Destabilizing	0.999	D	0.715	prob.delet.	D	0.556480371	None	None	N
Y/G	0.9856	likely_pathogenic	0.9874	pathogenic	-3.109	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
Y/H	0.952	likely_pathogenic	0.9406	pathogenic	-1.958	Destabilizing	1.0	D	0.797	deleterious	D	0.595876922	None	None	N
Y/I	0.9081	likely_pathogenic	0.886	pathogenic	-1.123	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
Y/K	0.9972	likely_pathogenic	0.9969	pathogenic	-2.12	Highly Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
Y/L	0.8259	likely_pathogenic	0.8173	pathogenic	-1.123	Destabilizing	0.999	D	0.788	deleterious	None	None	None	None	N
Y/M	0.944	likely_pathogenic	0.9387	pathogenic	-1.12	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
Y/N	0.9771	likely_pathogenic	0.9774	pathogenic	-2.976	Highly Destabilizing	1.0	D	0.846	deleterious	D	0.596078727	None	None	N
Y/P	0.9984	likely_pathogenic	0.9984	pathogenic	-1.645	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
Y/Q	0.9963	likely_pathogenic	0.9956	pathogenic	-2.576	Highly Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
Y/R	0.9913	likely_pathogenic	0.9903	pathogenic	-2.155	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
Y/S	0.9863	likely_pathogenic	0.9866	pathogenic	-3.429	Highly Destabilizing	1.0	D	0.857	deleterious	D	0.596078727	None	None	N
Y/T	0.9914	likely_pathogenic	0.9906	pathogenic	-3.046	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
Y/V	0.8924	likely_pathogenic	0.8758	pathogenic	-1.645	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
Y/W	0.6763	likely_pathogenic	0.6321	pathogenic	-0.188	Destabilizing	1.0	D	0.782	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.