TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29354	88285;88286;88287	chr2:178557094;178557093;178557092	chr2:179421821;179421820;179421819
N2AB	27713	83362;83363;83364	chr2:178557094;178557093;178557092	chr2:179421821;179421820;179421819
N2A	26786	80581;80582;80583	chr2:178557094;178557093;178557092	chr2:179421821;179421820;179421819
N2B	20289	61090;61091;61092	chr2:178557094;178557093;178557092	chr2:179421821;179421820;179421819
Novex-1	20414	61465;61466;61467	chr2:178557094;178557093;178557092	chr2:179421821;179421820;179421819
Novex-2	20481	61666;61667;61668	chr2:178557094;178557093;178557092	chr2:179421821;179421820;179421819
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-102
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.1305
• 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
L/V	None	None	0.989	N	0.654	0.316	0.372087925617	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
L/A	0.91	likely_pathogenic	0.8757	pathogenic	-2.378	Highly Destabilizing	0.983	D	0.706	prob.neutral	None	None	None	None	N
L/C	0.8438	likely_pathogenic	0.8048	pathogenic	-1.26	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
L/D	0.9993	likely_pathogenic	0.999	pathogenic	-2.924	Highly Destabilizing	0.99	D	0.901	deleterious	None	None	None	None	N
L/E	0.9956	likely_pathogenic	0.9941	pathogenic	-2.587	Highly Destabilizing	0.995	D	0.903	deleterious	None	None	None	None	N
L/F	0.4845	ambiguous	0.3863	ambiguous	-1.417	Destabilizing	0.999	D	0.747	deleterious	D	0.537864457	None	None	N
L/G	0.9892	likely_pathogenic	0.9835	pathogenic	-2.982	Highly Destabilizing	0.99	D	0.865	deleterious	None	None	None	None	N
L/H	0.9836	likely_pathogenic	0.9793	pathogenic	-2.911	Highly Destabilizing	0.999	D	0.915	deleterious	D	0.562262589	None	None	N
L/I	0.0959	likely_benign	0.0824	benign	-0.545	Destabilizing	0.996	D	0.635	neutral	N	0.511014112	None	None	N
L/K	0.9902	likely_pathogenic	0.9892	pathogenic	-1.631	Destabilizing	0.995	D	0.865	deleterious	None	None	None	None	N
L/M	0.2501	likely_benign	0.2197	benign	-0.724	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
L/N	0.9951	likely_pathogenic	0.9936	pathogenic	-2.43	Highly Destabilizing	0.289	N	0.758	deleterious	None	None	None	None	N
L/P	0.9956	likely_pathogenic	0.9941	pathogenic	-1.15	Destabilizing	0.999	D	0.917	deleterious	D	0.562009099	None	None	N
L/Q	0.9785	likely_pathogenic	0.9734	pathogenic	-1.96	Destabilizing	0.998	D	0.896	deleterious	None	None	None	None	N
L/R	0.9819	likely_pathogenic	0.9771	pathogenic	-2.004	Highly Destabilizing	0.993	D	0.89	deleterious	D	0.562009099	None	None	N
L/S	0.9878	likely_pathogenic	0.9816	pathogenic	-2.856	Highly Destabilizing	0.99	D	0.832	deleterious	None	None	None	None	N
L/T	0.941	likely_pathogenic	0.9219	pathogenic	-2.346	Highly Destabilizing	0.995	D	0.755	deleterious	None	None	None	None	N
L/V	0.1247	likely_benign	0.1062	benign	-1.15	Destabilizing	0.989	D	0.654	neutral	N	0.480262192	None	None	N
L/W	0.9522	likely_pathogenic	0.9322	pathogenic	-1.732	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/Y	0.9418	likely_pathogenic	0.9214	pathogenic	-1.563	Destabilizing	0.999	D	0.803	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.