TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15363	46312;46313;46314	chr2:178620434;178620433;178620432	chr2:179485161;179485160;179485159
N2AB	13722	41389;41390;41391	chr2:178620434;178620433;178620432	chr2:179485161;179485160;179485159
N2A	12795	38608;38609;38610	chr2:178620434;178620433;178620432	chr2:179485161;179485160;179485159
N2B	6298	19117;19118;19119	chr2:178620434;178620433;178620432	chr2:179485161;179485160;179485159
Novex-1	6423	19492;19493;19494	chr2:178620434;178620433;178620432	chr2:179485161;179485160;179485159
Novex-2	6490	19693;19694;19695	chr2:178620434;178620433;178620432	chr2:179485161;179485160;179485159
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-105
• Domain position: 62
• Structural Position: 144
• Q(SASA): 0.0622
• 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
C/G	None	None	0.698	D	0.695	0.467	0.831465730767	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	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	0.6249	likely_pathogenic	0.5596	ambiguous	-0.945	Destabilizing	0.559	D	0.441	neutral	None	None	None	None	N
C/D	0.9931	likely_pathogenic	0.992	pathogenic	-1.375	Destabilizing	0.956	D	0.742	deleterious	None	None	None	None	N
C/E	0.9971	likely_pathogenic	0.9964	pathogenic	-1.247	Destabilizing	0.956	D	0.746	deleterious	None	None	None	None	N
C/F	0.8831	likely_pathogenic	0.8964	pathogenic	-0.891	Destabilizing	0.97	D	0.711	prob.delet.	D	0.614105393	None	None	N
C/G	0.6198	likely_pathogenic	0.5406	ambiguous	-1.214	Destabilizing	0.698	D	0.695	prob.neutral	D	0.573970628	None	None	N
C/H	0.987	likely_pathogenic	0.9878	pathogenic	-1.783	Destabilizing	0.998	D	0.739	prob.delet.	None	None	None	None	N
C/I	0.7876	likely_pathogenic	0.8069	pathogenic	-0.282	Destabilizing	0.978	D	0.695	prob.neutral	None	None	None	None	N
C/K	0.9975	likely_pathogenic	0.9973	pathogenic	-0.583	Destabilizing	0.956	D	0.739	prob.delet.	None	None	None	None	N
C/L	0.8349	likely_pathogenic	0.8181	pathogenic	-0.282	Destabilizing	0.86	D	0.595	neutral	None	None	None	None	N
C/M	0.9331	likely_pathogenic	0.9263	pathogenic	0.203	Stabilizing	0.998	D	0.676	prob.neutral	None	None	None	None	N
C/N	0.9686	likely_pathogenic	0.9616	pathogenic	-0.918	Destabilizing	0.956	D	0.749	deleterious	None	None	None	None	N
C/P	0.9799	likely_pathogenic	0.9827	pathogenic	-0.476	Destabilizing	0.978	D	0.759	deleterious	None	None	None	None	N
C/Q	0.9915	likely_pathogenic	0.9909	pathogenic	-0.815	Destabilizing	0.956	D	0.758	deleterious	None	None	None	None	N
C/R	0.978	likely_pathogenic	0.9792	pathogenic	-0.784	Destabilizing	0.942	D	0.751	deleterious	D	0.573970628	None	None	N
C/S	0.6777	likely_pathogenic	0.6192	pathogenic	-1.107	Destabilizing	0.058	N	0.451	neutral	N	0.507704101	None	None	N
C/T	0.6927	likely_pathogenic	0.6037	pathogenic	-0.822	Destabilizing	0.754	D	0.618	neutral	None	None	None	None	N
C/V	0.6025	likely_pathogenic	0.596	pathogenic	-0.476	Destabilizing	0.86	D	0.65	neutral	None	None	None	None	N
C/W	0.9821	likely_pathogenic	0.985	pathogenic	-1.25	Destabilizing	0.997	D	0.699	prob.neutral	D	0.615971616	None	None	N
C/Y	0.9655	likely_pathogenic	0.9685	pathogenic	-0.912	Destabilizing	0.99	D	0.723	prob.delet.	D	0.61478752	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.