TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23571	70936;70937;70938	chr2:178575421;178575420;178575419	chr2:179440148;179440147;179440146
N2AB	21930	66013;66014;66015	chr2:178575421;178575420;178575419	chr2:179440148;179440147;179440146
N2A	21003	63232;63233;63234	chr2:178575421;178575420;178575419	chr2:179440148;179440147;179440146
N2B	14506	43741;43742;43743	chr2:178575421;178575420;178575419	chr2:179440148;179440147;179440146
Novex-1	14631	44116;44117;44118	chr2:178575421;178575420;178575419	chr2:179440148;179440147;179440146
Novex-2	14698	44317;44318;44319	chr2:178575421;178575420;178575419	chr2:179440148;179440147;179440146
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-59
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.1111
• 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
A/T	None	None	0.971	N	0.685	0.21	0.246773566709	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
A/C	0.4968	ambiguous	0.4729	ambiguous	-0.662	Destabilizing	0.998	D	0.737	prob.delet.	None	None	None	None	N
A/D	0.9551	likely_pathogenic	0.9446	pathogenic	-2.248	Highly Destabilizing	0.942	D	0.767	deleterious	N	0.490144603	None	None	N
A/E	0.8291	likely_pathogenic	0.8154	pathogenic	-1.99	Destabilizing	0.978	D	0.721	prob.delet.	None	None	None	None	N
A/F	0.5272	ambiguous	0.442	ambiguous	-0.408	Destabilizing	0.915	D	0.762	deleterious	None	None	None	None	N
A/G	0.2224	likely_benign	0.2085	benign	-1.352	Destabilizing	0.014	N	0.384	neutral	N	0.505301648	None	None	N
A/H	0.8399	likely_pathogenic	0.8111	pathogenic	-1.973	Destabilizing	0.988	D	0.765	deleterious	None	None	None	None	N
A/I	0.4556	ambiguous	0.3934	ambiguous	0.566	Stabilizing	0.956	D	0.737	prob.delet.	None	None	None	None	N
A/K	0.8756	likely_pathogenic	0.8687	pathogenic	-0.718	Destabilizing	0.956	D	0.721	prob.delet.	None	None	None	None	N
A/L	0.3262	likely_benign	0.2892	benign	0.566	Stabilizing	0.754	D	0.706	prob.neutral	None	None	None	None	N
A/M	0.286	likely_benign	0.2594	benign	0.175	Stabilizing	0.998	D	0.729	prob.delet.	None	None	None	None	N
A/N	0.8257	likely_pathogenic	0.7912	pathogenic	-1.189	Destabilizing	0.956	D	0.752	deleterious	None	None	None	None	N
A/P	0.9901	likely_pathogenic	0.9881	pathogenic	0.137	Stabilizing	0.99	D	0.724	prob.delet.	N	0.508533954	None	None	N
A/Q	0.6894	likely_pathogenic	0.688	pathogenic	-0.867	Destabilizing	0.978	D	0.726	prob.delet.	None	None	None	None	N
A/R	0.8198	likely_pathogenic	0.8165	pathogenic	-1.072	Destabilizing	0.978	D	0.725	prob.delet.	None	None	None	None	N
A/S	0.198	likely_benign	0.1766	benign	-1.527	Destabilizing	0.822	D	0.595	neutral	N	0.483232865	None	None	N
A/T	0.2317	likely_benign	0.1897	benign	-1.141	Destabilizing	0.971	D	0.685	prob.neutral	N	0.496623449	None	None	N
A/V	0.2416	likely_benign	0.2	benign	0.137	Stabilizing	0.822	D	0.649	neutral	N	0.458969138	None	None	N
A/W	0.8775	likely_pathogenic	0.8607	pathogenic	-1.312	Destabilizing	0.994	D	0.807	deleterious	None	None	None	None	N
A/Y	0.6399	likely_pathogenic	0.5889	pathogenic	-0.69	Destabilizing	0.043	N	0.666	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.