TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30862	92809;92810;92811	chr2:178549042;178549041;178549040	chr2:179413769;179413768;179413767
N2AB	29221	87886;87887;87888	chr2:178549042;178549041;178549040	chr2:179413769;179413768;179413767
N2A	28294	85105;85106;85107	chr2:178549042;178549041;178549040	chr2:179413769;179413768;179413767
N2B	21797	65614;65615;65616	chr2:178549042;178549041;178549040	chr2:179413769;179413768;179413767
Novex-1	21922	65989;65990;65991	chr2:178549042;178549041;178549040	chr2:179413769;179413768;179413767
Novex-2	21989	66190;66191;66192	chr2:178549042;178549041;178549040	chr2:179413769;179413768;179413767
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-113
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.2911
• 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
K/N	None	None	0.99	N	0.691	0.274	0.198526703765	gnomAD-4.0.0	2.05253E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69828E-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
K/A	0.5099	ambiguous	0.5068	ambiguous	-0.797	Destabilizing	0.86	D	0.483	neutral	None	None	None	None	N
K/C	0.8039	likely_pathogenic	0.8091	pathogenic	-0.638	Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
K/D	0.7705	likely_pathogenic	0.7497	pathogenic	-0.395	Destabilizing	0.993	D	0.769	deleterious	None	None	None	None	N
K/E	0.2775	likely_benign	0.2592	benign	-0.256	Destabilizing	0.904	D	0.465	neutral	N	0.405174726	None	None	N
K/F	0.9102	likely_pathogenic	0.9039	pathogenic	-0.359	Destabilizing	0.915	D	0.809	deleterious	None	None	None	None	N
K/G	0.6607	likely_pathogenic	0.6663	pathogenic	-1.204	Destabilizing	0.978	D	0.643	neutral	None	None	None	None	N
K/H	0.4702	ambiguous	0.4624	ambiguous	-1.569	Destabilizing	0.998	D	0.742	deleterious	None	None	None	None	N
K/I	0.5637	ambiguous	0.5449	ambiguous	0.277	Stabilizing	0.915	D	0.735	prob.delet.	None	None	None	None	N
K/L	0.4826	ambiguous	0.4712	ambiguous	0.277	Stabilizing	0.019	N	0.372	neutral	None	None	None	None	N
K/M	0.3704	ambiguous	0.3567	ambiguous	0.229	Stabilizing	0.942	D	0.773	deleterious	N	0.478156414	None	None	N
K/N	0.6678	likely_pathogenic	0.6333	pathogenic	-0.694	Destabilizing	0.99	D	0.691	prob.neutral	N	0.502069341	None	None	N
K/P	0.6445	likely_pathogenic	0.6492	pathogenic	-0.051	Destabilizing	0.993	D	0.788	deleterious	None	None	None	None	N
K/Q	0.1843	likely_benign	0.1849	benign	-0.7	Destabilizing	0.99	D	0.682	prob.neutral	N	0.487926608	None	None	N
K/R	0.0883	likely_benign	0.091	benign	-0.824	Destabilizing	0.904	D	0.496	neutral	N	0.447101493	None	None	N
K/S	0.6479	likely_pathogenic	0.6406	pathogenic	-1.339	Destabilizing	0.926	D	0.524	neutral	None	None	None	None	N
K/T	0.3783	ambiguous	0.3595	ambiguous	-0.976	Destabilizing	0.942	D	0.651	neutral	N	0.472901228	None	None	N
K/V	0.4809	ambiguous	0.4739	ambiguous	-0.051	Destabilizing	0.754	D	0.569	neutral	None	None	None	None	N
K/W	0.8975	likely_pathogenic	0.9	pathogenic	-0.239	Destabilizing	0.998	D	0.767	deleterious	None	None	None	None	N
K/Y	0.8326	likely_pathogenic	0.823	pathogenic	0.028	Stabilizing	0.978	D	0.786	deleterious	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.