TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27477	82654;82655;82656	chr2:178563703;178563702;178563701	chr2:179428430;179428429;179428428
N2AB	25836	77731;77732;77733	chr2:178563703;178563702;178563701	chr2:179428430;179428429;179428428
N2A	24909	74950;74951;74952	chr2:178563703;178563702;178563701	chr2:179428430;179428429;179428428
N2B	18412	55459;55460;55461	chr2:178563703;178563702;178563701	chr2:179428430;179428429;179428428
Novex-1	18537	55834;55835;55836	chr2:178563703;178563702;178563701	chr2:179428430;179428429;179428428
Novex-2	18604	56035;56036;56037	chr2:178563703;178563702;178563701	chr2:179428430;179428429;179428428
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: Fn3-88
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.4445
• 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/D	None	None	0.822	N	0.51	0.165	0.32980341726	gnomAD-4.0.0	1.59118E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43283E-05	0
E/G	rs1184828155	-1.173	0.014	N	0.4	0.281	0.27132560031	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/G	rs1184828155	-1.173	0.014	N	0.4	0.281	0.27132560031	gnomAD-4.0.0	1.59122E-06	None	None	None	None	I	None	0	2.28645E-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	0.1858	likely_benign	0.2075	benign	-0.738	Destabilizing	0.698	D	0.603	neutral	N	0.481154927	None	None	I
E/C	0.8276	likely_pathogenic	0.8571	pathogenic	-0.192	Destabilizing	0.998	D	0.803	deleterious	None	None	None	None	I
E/D	0.1604	likely_benign	0.194	benign	-0.685	Destabilizing	0.822	D	0.51	neutral	N	0.484535515	None	None	I
E/F	0.7514	likely_pathogenic	0.7996	pathogenic	-0.437	Destabilizing	0.956	D	0.785	deleterious	None	None	None	None	I
E/G	0.3034	likely_benign	0.3286	benign	-1.007	Destabilizing	0.014	N	0.4	neutral	N	0.501994661	None	None	I
E/H	0.4662	ambiguous	0.5194	ambiguous	-0.463	Destabilizing	0.998	D	0.589	neutral	None	None	None	None	I
E/I	0.3005	likely_benign	0.3476	ambiguous	-0.034	Destabilizing	0.915	D	0.704	prob.neutral	None	None	None	None	I
E/K	0.1773	likely_benign	0.1954	benign	0.005	Stabilizing	0.822	D	0.535	neutral	N	0.506298938	None	None	I
E/L	0.3889	ambiguous	0.4458	ambiguous	-0.034	Destabilizing	0.754	D	0.665	neutral	None	None	None	None	I
E/M	0.4189	ambiguous	0.4757	ambiguous	0.266	Stabilizing	0.994	D	0.765	deleterious	None	None	None	None	I
E/N	0.2967	likely_benign	0.3515	ambiguous	-0.428	Destabilizing	0.956	D	0.564	neutral	None	None	None	None	I
E/P	0.9424	likely_pathogenic	0.9463	pathogenic	-0.248	Destabilizing	0.993	D	0.727	prob.delet.	None	None	None	None	I
E/Q	0.1443	likely_benign	0.1551	benign	-0.368	Destabilizing	0.99	D	0.573	neutral	N	0.464897097	None	None	I
E/R	0.2947	likely_benign	0.324	benign	0.218	Stabilizing	0.978	D	0.591	neutral	None	None	None	None	I
E/S	0.2196	likely_benign	0.2565	benign	-0.624	Destabilizing	0.86	D	0.525	neutral	None	None	None	None	I
E/T	0.2072	likely_benign	0.237	benign	-0.4	Destabilizing	0.86	D	0.649	neutral	None	None	None	None	I
E/V	0.1707	likely_benign	0.1946	benign	-0.248	Destabilizing	0.032	N	0.415	neutral	N	0.496796808	None	None	I
E/W	0.914	likely_pathogenic	0.9319	pathogenic	-0.19	Destabilizing	0.998	D	0.771	deleterious	None	None	None	None	I
E/Y	0.6637	likely_pathogenic	0.7056	pathogenic	-0.171	Destabilizing	0.978	D	0.782	deleterious	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.