TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21391	64396;64397;64398	chr2:178586730;178586729;178586728	chr2:179451457;179451456;179451455
N2AB	19750	59473;59474;59475	chr2:178586730;178586729;178586728	chr2:179451457;179451456;179451455
N2A	18823	56692;56693;56694	chr2:178586730;178586729;178586728	chr2:179451457;179451456;179451455
N2B	12326	37201;37202;37203	chr2:178586730;178586729;178586728	chr2:179451457;179451456;179451455
Novex-1	12451	37576;37577;37578	chr2:178586730;178586729;178586728	chr2:179451457;179451456;179451455
Novex-2	12518	37777;37778;37779	chr2:178586730;178586729;178586728	chr2:179451457;179451456;179451455
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-43
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.8469
• 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
L/R	None	None	1.0	N	0.704	0.469	0.682517699708	gnomAD-4.0.0	1.59276E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43332E-05	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
L/A	0.4025	ambiguous	0.3219	benign	-0.557	Destabilizing	0.999	D	0.619	neutral	None	None	None	None	I
L/C	0.8264	likely_pathogenic	0.7654	pathogenic	-0.496	Destabilizing	1.0	D	0.613	neutral	None	None	None	None	I
L/D	0.8562	likely_pathogenic	0.7764	pathogenic	-0.473	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
L/E	0.5358	ambiguous	0.4292	ambiguous	-0.574	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
L/F	0.363	ambiguous	0.2958	benign	-0.648	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	I
L/G	0.7632	likely_pathogenic	0.6705	pathogenic	-0.703	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
L/H	0.5628	ambiguous	0.4659	ambiguous	-0.014	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
L/I	0.1724	likely_benign	0.1473	benign	-0.295	Destabilizing	0.999	D	0.471	neutral	N	0.480251275	None	None	I
L/K	0.4985	ambiguous	0.3984	ambiguous	-0.357	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
L/M	0.1947	likely_benign	0.1676	benign	-0.392	Destabilizing	1.0	D	0.595	neutral	None	None	None	None	I
L/N	0.6233	likely_pathogenic	0.5064	ambiguous	-0.106	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
L/P	0.5764	likely_pathogenic	0.4903	ambiguous	-0.35	Destabilizing	1.0	D	0.703	prob.neutral	N	0.471514361	None	None	I
L/Q	0.2829	likely_benign	0.2192	benign	-0.362	Destabilizing	1.0	D	0.678	prob.neutral	N	0.488542684	None	None	I
L/R	0.483	ambiguous	0.4009	ambiguous	0.233	Stabilizing	1.0	D	0.704	prob.neutral	N	0.471514361	None	None	I
L/S	0.5324	ambiguous	0.4241	ambiguous	-0.471	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
L/T	0.4647	ambiguous	0.3718	ambiguous	-0.471	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
L/V	0.1602	likely_benign	0.1401	benign	-0.35	Destabilizing	0.999	D	0.537	neutral	N	0.46787941	None	None	I
L/W	0.5599	ambiguous	0.4927	ambiguous	-0.673	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
L/Y	0.5994	likely_pathogenic	0.5131	ambiguous	-0.424	Destabilizing	1.0	D	0.664	neutral	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.