TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28502	85729;85730;85731	chr2:178560628;178560627;178560626	chr2:179425355;179425354;179425353
N2AB	26861	80806;80807;80808	chr2:178560628;178560627;178560626	chr2:179425355;179425354;179425353
N2A	25934	78025;78026;78027	chr2:178560628;178560627;178560626	chr2:179425355;179425354;179425353
N2B	19437	58534;58535;58536	chr2:178560628;178560627;178560626	chr2:179425355;179425354;179425353
Novex-1	19562	58909;58910;58911	chr2:178560628;178560627;178560626	chr2:179425355;179425354;179425353
Novex-2	19629	59110;59111;59112	chr2:178560628;178560627;178560626	chr2:179425355;179425354;179425353
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-95
• Domain position: 53
• Structural Position: 69
• Q(SASA): 0.4206
• Predicted PPI site: I

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
E/G	None	None	0.92	N	0.505	0.191	0.402471007487	gnomAD-4.0.0	3.18351E-06	None	None	None	None	I	None	0	4.57415E-05	None	0	0	None	0	0	0	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
E/A	0.1363	likely_benign	0.1445	benign	-0.454	Destabilizing	0.134	N	0.268	neutral	N	0.397846109	None	None	I
E/C	0.6768	likely_pathogenic	0.7278	pathogenic	-0.11	Destabilizing	0.999	D	0.56	neutral	None	None	None	None	I
E/D	0.1597	likely_benign	0.1703	benign	-0.599	Destabilizing	0.959	D	0.357	neutral	N	0.429745096	None	None	I
E/F	0.6982	likely_pathogenic	0.7276	pathogenic	-0.124	Destabilizing	0.884	D	0.552	neutral	None	None	None	None	I
E/G	0.1797	likely_benign	0.1748	benign	-0.733	Destabilizing	0.92	D	0.505	neutral	N	0.439578088	None	None	I
E/H	0.3235	likely_benign	0.3491	ambiguous	-0.144	Destabilizing	0.982	D	0.442	neutral	None	None	None	None	I
E/I	0.3842	ambiguous	0.4279	ambiguous	0.273	Stabilizing	0.991	D	0.561	neutral	None	None	None	None	I
E/K	0.1	likely_benign	0.0985	benign	0.117	Stabilizing	0.959	D	0.375	neutral	N	0.499605039	None	None	I
E/L	0.3782	ambiguous	0.4087	ambiguous	0.273	Stabilizing	0.939	D	0.511	neutral	None	None	None	None	I
E/M	0.4333	ambiguous	0.4669	ambiguous	0.451	Stabilizing	0.999	D	0.548	neutral	None	None	None	None	I
E/N	0.2645	likely_benign	0.2811	benign	-0.332	Destabilizing	0.997	D	0.411	neutral	None	None	None	None	I
E/P	0.6963	likely_pathogenic	0.7268	pathogenic	0.053	Stabilizing	0.991	D	0.523	neutral	None	None	None	None	I
E/Q	0.1126	likely_benign	0.1157	benign	-0.242	Destabilizing	0.986	D	0.416	neutral	N	0.507320446	None	None	I
E/R	0.1692	likely_benign	0.1668	benign	0.335	Stabilizing	0.991	D	0.411	neutral	None	None	None	None	I
E/S	0.1721	likely_benign	0.179	benign	-0.516	Destabilizing	0.884	D	0.357	neutral	None	None	None	None	I
E/T	0.1883	likely_benign	0.214	benign	-0.285	Destabilizing	0.939	D	0.485	neutral	None	None	None	None	I
E/V	0.2072	likely_benign	0.2334	benign	0.053	Stabilizing	0.92	D	0.507	neutral	N	0.497066167	None	None	I
E/W	0.8551	likely_pathogenic	0.8617	pathogenic	0.077	Stabilizing	0.998	D	0.558	neutral	None	None	None	None	I
E/Y	0.547	ambiguous	0.5804	pathogenic	0.133	Stabilizing	0.079	N	0.287	neutral	None	None	None	None	I

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.