TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4909	14950;14951;14952	chr2:178735721;178735720;178735719	chr2:179600448;179600447;179600446
N2AB	4592	13999;14000;14001	chr2:178735721;178735720;178735719	chr2:179600448;179600447;179600446
N2A	3665	11218;11219;11220	chr2:178735721;178735720;178735719	chr2:179600448;179600447;179600446
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-32
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.0841
• Site annotation: disulfide
• 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/F	None	None	0.859	D	0.87	0.487	0.776434072436	gnomAD-4.0.0	6.84226E-07	None	None	disulfide	None	N	None	0	0	None	0	0	None	0	0	8.99454E-07	0	0
C/Y	rs188073989	None	0.859	N	0.88	0.532	0.663756110175	gnomAD-4.0.0	6.84226E-07	None	None	disulfide	None	N	None	0	0	None	0	0	None	0	0	8.99454E-07	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	0.4496	ambiguous	0.4721	ambiguous	-1.774	Destabilizing	0.072	N	0.658	neutral	None	None	disulfide	None	N
C/D	0.9789	likely_pathogenic	0.9851	pathogenic	-1.773	Destabilizing	0.567	D	0.881	deleterious	None	None	disulfide	None	N
C/E	0.9897	likely_pathogenic	0.9927	pathogenic	-1.54	Destabilizing	0.726	D	0.901	deleterious	None	None	disulfide	None	N
C/F	0.4319	ambiguous	0.4702	ambiguous	-1.042	Destabilizing	0.859	D	0.87	deleterious	D	0.547539872	disulfide	None	N
C/G	0.167	likely_benign	0.1831	benign	-2.121	Highly Destabilizing	None	N	0.649	neutral	N	0.495890613	disulfide	None	N
C/H	0.96	likely_pathogenic	0.9703	pathogenic	-2.229	Highly Destabilizing	0.968	D	0.899	deleterious	None	None	disulfide	None	N
C/I	0.5597	ambiguous	0.6012	pathogenic	-0.824	Destabilizing	0.726	D	0.825	deleterious	None	None	disulfide	None	N
C/K	0.9935	likely_pathogenic	0.9951	pathogenic	-1.489	Destabilizing	0.567	D	0.887	deleterious	None	None	disulfide	None	N
C/L	0.6053	likely_pathogenic	0.6333	pathogenic	-0.824	Destabilizing	0.272	N	0.791	deleterious	None	None	disulfide	None	N
C/M	0.7673	likely_pathogenic	0.7965	pathogenic	-0.064	Destabilizing	0.968	D	0.824	deleterious	None	None	disulfide	None	N
C/N	0.9156	likely_pathogenic	0.9353	pathogenic	-2.062	Highly Destabilizing	0.567	D	0.887	deleterious	None	None	disulfide	None	N
C/P	0.9925	likely_pathogenic	0.9946	pathogenic	-1.121	Destabilizing	0.726	D	0.902	deleterious	None	None	disulfide	None	N
C/Q	0.9788	likely_pathogenic	0.9833	pathogenic	-1.602	Destabilizing	0.726	D	0.905	deleterious	None	None	disulfide	None	N
C/R	0.9621	likely_pathogenic	0.9698	pathogenic	-1.783	Destabilizing	0.667	D	0.895	deleterious	D	0.54859	disulfide	None	N
C/S	0.5008	ambiguous	0.54	ambiguous	-2.382	Highly Destabilizing	0.124	N	0.785	deleterious	N	0.498819336	disulfide	None	N
C/T	0.6456	likely_pathogenic	0.6806	pathogenic	-1.98	Destabilizing	0.272	N	0.821	deleterious	None	None	disulfide	None	N
C/V	0.4469	ambiguous	0.4683	ambiguous	-1.121	Destabilizing	0.431	N	0.816	deleterious	None	None	disulfide	None	N
C/W	0.8757	likely_pathogenic	0.8979	pathogenic	-1.459	Destabilizing	0.958	D	0.883	deleterious	D	0.54859	disulfide	None	N
C/Y	0.6643	likely_pathogenic	0.7075	pathogenic	-1.284	Destabilizing	0.859	D	0.88	deleterious	N	0.388467375	disulfide	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.