TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17885	53878;53879;53880	chr2:178605642;178605641;178605640	chr2:179470369;179470368;179470367
N2AB	16244	48955;48956;48957	chr2:178605642;178605641;178605640	chr2:179470369;179470368;179470367
N2A	15317	46174;46175;46176	chr2:178605642;178605641;178605640	chr2:179470369;179470368;179470367
N2B	8820	26683;26684;26685	chr2:178605642;178605641;178605640	chr2:179470369;179470368;179470367
Novex-1	8945	27058;27059;27060	chr2:178605642;178605641;178605640	chr2:179470369;179470368;179470367
Novex-2	9012	27259;27260;27261	chr2:178605642;178605641;178605640	chr2:179470369;179470368;179470367
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-18
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.5883
• 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
E/Q	None	None	0.301	N	0.449	0.069	0.17948927462	gnomAD-4.0.0	6.85348E-07	None	None	None	None	N	None	2.99778E-05	0	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	0.1314	likely_benign	0.1051	benign	-0.133	Destabilizing	None	N	0.208	neutral	N	0.373774383	None	None	N
E/C	0.841	likely_pathogenic	0.7975	pathogenic	-0.371	Destabilizing	0.883	D	0.451	neutral	None	None	None	None	N
E/D	0.236	likely_benign	0.2003	benign	-0.901	Destabilizing	0.081	N	0.421	neutral	N	0.47628825	None	None	N
E/F	0.8289	likely_pathogenic	0.7468	pathogenic	0.546	Stabilizing	0.667	D	0.493	neutral	None	None	None	None	N
E/G	0.3303	likely_benign	0.2636	benign	-0.454	Destabilizing	0.042	N	0.382	neutral	N	0.438327294	None	None	N
E/H	0.6757	likely_pathogenic	0.5704	pathogenic	0.782	Stabilizing	0.859	D	0.528	neutral	None	None	None	None	N
E/I	0.3572	ambiguous	0.2589	benign	0.72	Stabilizing	0.124	N	0.465	neutral	None	None	None	None	N
E/K	0.2934	likely_benign	0.2313	benign	0.088	Stabilizing	0.081	N	0.425	neutral	N	0.383492732	None	None	N
E/L	0.3557	ambiguous	0.2853	benign	0.72	Stabilizing	0.055	N	0.368	neutral	None	None	None	None	N
E/M	0.4443	ambiguous	0.3491	ambiguous	0.602	Stabilizing	0.667	D	0.485	neutral	None	None	None	None	N
E/N	0.4527	ambiguous	0.34	ambiguous	-0.652	Destabilizing	0.364	N	0.479	neutral	None	None	None	None	N
E/P	0.175	likely_benign	0.1385	benign	0.458	Stabilizing	None	N	0.215	neutral	None	None	None	None	N
E/Q	0.1913	likely_benign	0.155	benign	-0.488	Destabilizing	0.301	N	0.449	neutral	N	0.430246529	None	None	N
E/R	0.4536	ambiguous	0.3703	ambiguous	0.512	Stabilizing	0.22	N	0.477	neutral	None	None	None	None	N
E/S	0.3186	likely_benign	0.2323	benign	-0.818	Destabilizing	0.055	N	0.403	neutral	None	None	None	None	N
E/T	0.3095	likely_benign	0.2159	benign	-0.526	Destabilizing	0.104	N	0.399	neutral	None	None	None	None	N
E/V	0.2248	likely_benign	0.1656	benign	0.458	Stabilizing	0.001	N	0.291	neutral	N	0.444349189	None	None	N
E/W	0.9573	likely_pathogenic	0.9267	pathogenic	0.769	Stabilizing	0.958	D	0.495	neutral	None	None	None	None	N
E/Y	0.7284	likely_pathogenic	0.6344	pathogenic	0.826	Stabilizing	0.859	D	0.513	neutral	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.