TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5466	16621;16622;16623	chr2:178732665;178732664;178732663	chr2:179597392;179597391;179597390
N2AB	5149	15670;15671;15672	chr2:178732665;178732664;178732663	chr2:179597392;179597391;179597390
N2A	4222	12889;12890;12891	chr2:178732665;178732664;178732663	chr2:179597392;179597391;179597390
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-38
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.4011
• 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
A/T	None	None	0.001	N	0.101	0.063	0.0846915920261	gnomAD-4.0.0	1.37218E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.80233E-06	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	0.4327	ambiguous	0.4566	ambiguous	-0.723	Destabilizing	0.973	D	0.456	neutral	None	None	None	None	I
A/D	0.2068	likely_benign	0.2495	benign	0.031	Stabilizing	0.826	D	0.478	neutral	None	None	None	None	I
A/E	0.1772	likely_benign	0.2227	benign	-0.047	Destabilizing	0.505	D	0.425	neutral	N	0.422863904	None	None	I
A/F	0.2149	likely_benign	0.249	benign	-0.606	Destabilizing	0.826	D	0.563	neutral	None	None	None	None	I
A/G	0.1351	likely_benign	0.1482	benign	-0.5	Destabilizing	0.505	D	0.375	neutral	N	0.466636111	None	None	I
A/H	0.2998	likely_benign	0.3469	ambiguous	-0.428	Destabilizing	0.991	D	0.544	neutral	None	None	None	None	I
A/I	0.1464	likely_benign	0.1721	benign	-0.089	Destabilizing	0.189	N	0.387	neutral	None	None	None	None	I
A/K	0.2271	likely_benign	0.2821	benign	-0.577	Destabilizing	0.575	D	0.419	neutral	None	None	None	None	I
A/L	0.1214	likely_benign	0.1349	benign	-0.089	Destabilizing	0.218	N	0.432	neutral	None	None	None	None	I
A/M	0.1466	likely_benign	0.1624	benign	-0.33	Destabilizing	0.826	D	0.509	neutral	None	None	None	None	I
A/N	0.1611	likely_benign	0.1748	benign	-0.316	Destabilizing	0.826	D	0.539	neutral	None	None	None	None	I
A/P	0.1177	likely_benign	0.1271	benign	-0.134	Destabilizing	0.879	D	0.471	neutral	N	0.396832096	None	None	I
A/Q	0.231	likely_benign	0.2704	benign	-0.448	Destabilizing	0.906	D	0.515	neutral	None	None	None	None	I
A/R	0.2015	likely_benign	0.2476	benign	-0.27	Destabilizing	0.826	D	0.492	neutral	None	None	None	None	I
A/S	0.0829	likely_benign	0.084	benign	-0.683	Destabilizing	0.174	N	0.422	neutral	N	0.351366379	None	None	I
A/T	0.0675	likely_benign	0.0672	benign	-0.65	Destabilizing	0.001	N	0.101	neutral	N	0.363564885	None	None	I
A/V	0.0904	likely_benign	0.1026	benign	-0.134	Destabilizing	0.003	N	0.209	neutral	N	0.441855097	None	None	I
A/W	0.5309	ambiguous	0.5971	pathogenic	-0.829	Destabilizing	0.991	D	0.683	prob.neutral	None	None	None	None	I
A/Y	0.3137	likely_benign	0.3532	ambiguous	-0.434	Destabilizing	0.906	D	0.565	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.