TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29272	88039;88040;88041	chr2:178557448;178557447;178557446	chr2:179422175;179422174;179422173
N2AB	27631	83116;83117;83118	chr2:178557448;178557447;178557446	chr2:179422175;179422174;179422173
N2A	26704	80335;80336;80337	chr2:178557448;178557447;178557446	chr2:179422175;179422174;179422173
N2B	20207	60844;60845;60846	chr2:178557448;178557447;178557446	chr2:179422175;179422174;179422173
Novex-1	20332	61219;61220;61221	chr2:178557448;178557447;178557446	chr2:179422175;179422174;179422173
Novex-2	20399	61420;61421;61422	chr2:178557448;178557447;178557446	chr2:179422175;179422174;179422173
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: Fn3-101
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.0994
• 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/C	rs886039083	-1.933	1.0	D	0.874	0.879	0.882574075922	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	8.88E-06	0
Y/C	rs886039083	-1.933	1.0	D	0.874	0.879	0.882574075922	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	5.88E-05	0	0
Y/C	rs886039083	-1.933	1.0	D	0.874	0.879	0.882574075922	gnomAD-4.0.0	1.11534E-05	None	None	None	None	N	None	0	1.6665E-05	None	0	2.22856E-05	None	0	0	1.27134E-05	0	1.60102E-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
Y/A	0.9984	likely_pathogenic	0.9985	pathogenic	-3.898	Highly Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
Y/C	0.9147	likely_pathogenic	0.9369	pathogenic	-2.27	Highly Destabilizing	1.0	D	0.874	deleterious	D	0.65838814	None	None	N
Y/D	0.9986	likely_pathogenic	0.9985	pathogenic	-4.007	Highly Destabilizing	1.0	D	0.909	deleterious	D	0.658589944	None	None	N
Y/E	0.9996	likely_pathogenic	0.9996	pathogenic	-3.812	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
Y/F	0.2299	likely_benign	0.2105	benign	-1.652	Destabilizing	0.999	D	0.642	neutral	D	0.584379413	None	None	N
Y/G	0.9945	likely_pathogenic	0.9954	pathogenic	-4.263	Highly Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
Y/H	0.9818	likely_pathogenic	0.9811	pathogenic	-2.81	Highly Destabilizing	1.0	D	0.811	deleterious	D	0.657984531	None	None	N
Y/I	0.9863	likely_pathogenic	0.9844	pathogenic	-2.64	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
Y/K	0.9991	likely_pathogenic	0.9991	pathogenic	-2.782	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/L	0.9739	likely_pathogenic	0.9771	pathogenic	-2.64	Highly Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
Y/M	0.9911	likely_pathogenic	0.9915	pathogenic	-2.319	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
Y/N	0.9872	likely_pathogenic	0.9862	pathogenic	-3.475	Highly Destabilizing	1.0	D	0.891	deleterious	D	0.65838814	None	None	N
Y/P	0.9996	likely_pathogenic	0.9996	pathogenic	-3.08	Highly Destabilizing	1.0	D	0.934	deleterious	None	None	None	None	N
Y/Q	0.9989	likely_pathogenic	0.999	pathogenic	-3.266	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
Y/R	0.9966	likely_pathogenic	0.9967	pathogenic	-2.391	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/S	0.9923	likely_pathogenic	0.9928	pathogenic	-3.793	Highly Destabilizing	1.0	D	0.896	deleterious	D	0.65838814	None	None	N
Y/T	0.998	likely_pathogenic	0.9981	pathogenic	-3.498	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
Y/V	0.9801	likely_pathogenic	0.9789	pathogenic	-3.08	Highly Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
Y/W	0.8054	likely_pathogenic	0.8372	pathogenic	-0.873	Destabilizing	1.0	D	0.797	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.