TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6733	20422;20423;20424	chr2:178727168;178727167;178727166	chr2:179591895;179591894;179591893
N2AB	6416	19471;19472;19473	chr2:178727168;178727167;178727166	chr2:179591895;179591894;179591893
N2A	5489	16690;16691;16692	chr2:178727168;178727167;178727166	chr2:179591895;179591894;179591893
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-51
• Domain position: 67
• Structural Position: 148
• Q(SASA): 0.4301
• 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/D	rs374881285	0.176	0.001	N	0.195	0.14	0.12205267543	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	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	0.1359	likely_benign	0.1495	benign	-0.26	Destabilizing	0.876	D	0.514	neutral	N	0.460860356	None	None	N
E/C	0.8936	likely_pathogenic	0.9073	pathogenic	0.214	Stabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
E/D	0.0992	likely_benign	0.0943	benign	-0.097	Destabilizing	0.001	N	0.195	neutral	N	0.461163071	None	None	N
E/F	0.7676	likely_pathogenic	0.8062	pathogenic	-0.337	Destabilizing	0.999	D	0.671	neutral	None	None	None	None	N
E/G	0.1341	likely_benign	0.1547	benign	-0.387	Destabilizing	0.959	D	0.473	neutral	N	0.473217392	None	None	N
E/H	0.4507	ambiguous	0.5134	ambiguous	-0.092	Destabilizing	0.999	D	0.558	neutral	None	None	None	None	N
E/I	0.4424	ambiguous	0.4893	ambiguous	0.024	Stabilizing	0.983	D	0.692	prob.neutral	None	None	None	None	N
E/K	0.1256	likely_benign	0.1597	benign	0.619	Stabilizing	0.929	D	0.49	neutral	N	0.471406967	None	None	N
E/L	0.4429	ambiguous	0.4834	ambiguous	0.024	Stabilizing	0.983	D	0.669	neutral	None	None	None	None	N
E/M	0.4959	ambiguous	0.5408	ambiguous	0.187	Stabilizing	0.992	D	0.619	neutral	None	None	None	None	N
E/N	0.2289	likely_benign	0.2549	benign	0.376	Stabilizing	0.869	D	0.542	neutral	None	None	None	None	N
E/P	0.7555	likely_pathogenic	0.8006	pathogenic	-0.053	Destabilizing	0.896	D	0.59	neutral	None	None	None	None	N
E/Q	0.1506	likely_benign	0.1707	benign	0.395	Stabilizing	0.985	D	0.54	neutral	N	0.470432689	None	None	N
E/R	0.2235	likely_benign	0.2872	benign	0.629	Stabilizing	0.992	D	0.573	neutral	None	None	None	None	N
E/S	0.1688	likely_benign	0.1886	benign	0.252	Stabilizing	0.904	D	0.489	neutral	None	None	None	None	N
E/T	0.213	likely_benign	0.2381	benign	0.368	Stabilizing	0.989	D	0.54	neutral	None	None	None	None	N
E/V	0.2632	likely_benign	0.2921	benign	-0.053	Destabilizing	0.969	D	0.605	neutral	N	0.488323134	None	None	N
E/W	0.8647	likely_pathogenic	0.8978	pathogenic	-0.262	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
E/Y	0.6407	likely_pathogenic	0.6859	pathogenic	-0.112	Destabilizing	1.0	D	0.623	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.