TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15236	45931;45932;45933	chr2:178620904;178620903;178620902	chr2:179485631;179485630;179485629
N2AB	13595	41008;41009;41010	chr2:178620904;178620903;178620902	chr2:179485631;179485630;179485629
N2A	12668	38227;38228;38229	chr2:178620904;178620903;178620902	chr2:179485631;179485630;179485629
N2B	6171	18736;18737;18738	chr2:178620904;178620903;178620902	chr2:179485631;179485630;179485629
Novex-1	6296	19111;19112;19113	chr2:178620904;178620903;178620902	chr2:179485631;179485630;179485629
Novex-2	6363	19312;19313;19314	chr2:178620904;178620903;178620902	chr2:179485631;179485630;179485629
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: Ig-104
• Domain position: 29
• Structural Position: 44
• Q(SASA): 0.1416
• 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	0.034	N	0.437	0.12	0.208000267992	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	5.50964E-04	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
A/C	0.7748	likely_pathogenic	0.6884	pathogenic	-0.956	Destabilizing	0.996	D	0.705	prob.neutral	None	None	None	None	N
A/D	0.9666	likely_pathogenic	0.9491	pathogenic	-0.694	Destabilizing	0.901	D	0.719	prob.delet.	D	0.571207194	None	None	N
A/E	0.9388	likely_pathogenic	0.9145	pathogenic	-0.714	Destabilizing	0.923	D	0.696	prob.neutral	None	None	None	None	N
A/F	0.8742	likely_pathogenic	0.8149	pathogenic	-0.972	Destabilizing	0.961	D	0.737	prob.delet.	None	None	None	None	N
A/G	0.3925	ambiguous	0.3166	benign	-1.148	Destabilizing	0.565	D	0.655	neutral	N	0.486785155	None	None	N
A/H	0.9742	likely_pathogenic	0.963	pathogenic	-1.224	Destabilizing	0.989	D	0.715	prob.delet.	None	None	None	None	N
A/I	0.6553	likely_pathogenic	0.5434	ambiguous	-0.289	Destabilizing	0.633	D	0.685	prob.neutral	None	None	None	None	N
A/K	0.9845	likely_pathogenic	0.9754	pathogenic	-1.011	Destabilizing	0.858	D	0.697	prob.neutral	None	None	None	None	N
A/L	0.6148	likely_pathogenic	0.5139	ambiguous	-0.289	Destabilizing	0.633	D	0.649	neutral	None	None	None	None	N
A/M	0.7413	likely_pathogenic	0.6295	pathogenic	-0.317	Destabilizing	0.989	D	0.694	prob.neutral	None	None	None	None	N
A/N	0.9241	likely_pathogenic	0.8855	pathogenic	-0.737	Destabilizing	0.858	D	0.739	prob.delet.	None	None	None	None	N
A/P	0.8271	likely_pathogenic	0.82	pathogenic	-0.442	Destabilizing	0.949	D	0.726	prob.delet.	N	0.43122105	None	None	N
A/Q	0.9353	likely_pathogenic	0.9113	pathogenic	-0.848	Destabilizing	0.923	D	0.711	prob.delet.	None	None	None	None	N
A/R	0.9611	likely_pathogenic	0.9444	pathogenic	-0.737	Destabilizing	0.923	D	0.726	prob.delet.	None	None	None	None	N
A/S	0.2713	likely_benign	0.2267	benign	-1.181	Destabilizing	0.075	N	0.411	neutral	N	0.502614011	None	None	N
A/T	0.3655	ambiguous	0.2808	benign	-1.083	Destabilizing	0.034	N	0.437	neutral	N	0.473551019	None	None	N
A/V	0.3726	ambiguous	0.2853	benign	-0.442	Destabilizing	0.075	N	0.412	neutral	N	0.459199745	None	None	N
A/W	0.9853	likely_pathogenic	0.9781	pathogenic	-1.265	Destabilizing	0.996	D	0.739	prob.delet.	None	None	None	None	N
A/Y	0.9508	likely_pathogenic	0.9248	pathogenic	-0.856	Destabilizing	0.987	D	0.726	prob.delet.	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.