TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17428	52507;52508;52509	chr2:178608729;178608728;178608727	chr2:179473456;179473455;179473454
N2AB	15787	47584;47585;47586	chr2:178608729;178608728;178608727	chr2:179473456;179473455;179473454
N2A	14860	44803;44804;44805	chr2:178608729;178608728;178608727	chr2:179473456;179473455;179473454
N2B	8363	25312;25313;25314	chr2:178608729;178608728;178608727	chr2:179473456;179473455;179473454
Novex-1	8488	25687;25688;25689	chr2:178608729;178608728;178608727	chr2:179473456;179473455;179473454
Novex-2	8555	25888;25889;25890	chr2:178608729;178608728;178608727	chr2:179473456;179473455;179473454
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Fn3-14
• Domain position: 60
• Structural Position: 89
• Q(SASA): 0.3374
• 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
C/G	rs2055534842	None	1.0	N	0.791	0.378	0.78109972193	gnomAD-4.0.0	3.18769E-06	None	None	None	None	I	None	0	0	None	0	5.58098E-05	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
C/A	0.5398	ambiguous	0.5904	pathogenic	-1.659	Destabilizing	0.998	D	0.51	neutral	None	None	None	None	I
C/D	0.8558	likely_pathogenic	0.8901	pathogenic	-1.385	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	I
C/E	0.8658	likely_pathogenic	0.8988	pathogenic	-1.185	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
C/F	0.4968	ambiguous	0.5444	ambiguous	-1.095	Destabilizing	1.0	D	0.835	deleterious	N	0.504295996	None	None	I
C/G	0.238	likely_benign	0.2634	benign	-1.986	Destabilizing	1.0	D	0.791	deleterious	N	0.461512828	None	None	I
C/H	0.6452	likely_pathogenic	0.6765	pathogenic	-1.857	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
C/I	0.8319	likely_pathogenic	0.8499	pathogenic	-0.774	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	I
C/K	0.8197	likely_pathogenic	0.8525	pathogenic	-1.154	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
C/L	0.5404	ambiguous	0.5783	pathogenic	-0.774	Destabilizing	0.999	D	0.555	neutral	None	None	None	None	I
C/M	0.7286	likely_pathogenic	0.7677	pathogenic	0.316	Stabilizing	1.0	D	0.816	deleterious	None	None	None	None	I
C/N	0.5072	ambiguous	0.5506	ambiguous	-1.737	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	I
C/P	0.7263	likely_pathogenic	0.7695	pathogenic	-1.048	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
C/Q	0.6341	likely_pathogenic	0.6718	pathogenic	-1.4	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
C/R	0.5089	ambiguous	0.5343	ambiguous	-1.219	Destabilizing	1.0	D	0.832	deleterious	N	0.442111387	None	None	I
C/S	0.3853	ambiguous	0.4145	ambiguous	-2.099	Highly Destabilizing	1.0	D	0.744	deleterious	N	0.482765931	None	None	I
C/T	0.4165	ambiguous	0.4656	ambiguous	-1.723	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	I
C/V	0.6845	likely_pathogenic	0.7235	pathogenic	-1.048	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	I
C/W	0.7809	likely_pathogenic	0.8071	pathogenic	-1.33	Destabilizing	1.0	D	0.807	deleterious	N	0.468767756	None	None	I
C/Y	0.5548	ambiguous	0.6168	pathogenic	-1.199	Destabilizing	1.0	D	0.837	deleterious	N	0.490385336	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.