TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19763	59512;59513;59514	chr2:178592832;178592831;178592830	chr2:179457559;179457558;179457557
N2AB	18122	54589;54590;54591	chr2:178592832;178592831;178592830	chr2:179457559;179457558;179457557
N2A	17195	51808;51809;51810	chr2:178592832;178592831;178592830	chr2:179457559;179457558;179457557
N2B	10698	32317;32318;32319	chr2:178592832;178592831;178592830	chr2:179457559;179457558;179457557
Novex-1	10823	32692;32693;32694	chr2:178592832;178592831;178592830	chr2:179457559;179457558;179457557
Novex-2	10890	32893;32894;32895	chr2:178592832;178592831;178592830	chr2:179457559;179457558;179457557
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-31
• Domain position: 84
• Structural Position: 114
• Q(SASA): 0.5139
• 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	rs372951248	-0.406	1.0	N	0.799	0.389	None	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	8.9E-06	0
A/T	rs372951248	-0.406	1.0	N	0.799	0.389	None	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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	0.5838	likely_pathogenic	0.5822	pathogenic	-0.754	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
A/D	0.7968	likely_pathogenic	0.7926	pathogenic	-0.636	Destabilizing	1.0	D	0.877	deleterious	N	0.4851314	None	None	I
A/E	0.6196	likely_pathogenic	0.6086	pathogenic	-0.801	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	I
A/F	0.5477	ambiguous	0.556	ambiguous	-0.931	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	I
A/G	0.2453	likely_benign	0.2553	benign	-0.274	Destabilizing	1.0	D	0.633	neutral	N	0.472507647	None	None	I
A/H	0.8148	likely_pathogenic	0.8252	pathogenic	-0.253	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I
A/I	0.3206	likely_benign	0.331	benign	-0.382	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
A/K	0.8351	likely_pathogenic	0.8453	pathogenic	-0.606	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
A/L	0.4126	ambiguous	0.4168	ambiguous	-0.382	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
A/M	0.3853	ambiguous	0.3818	ambiguous	-0.409	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	I
A/N	0.6487	likely_pathogenic	0.6574	pathogenic	-0.273	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	I
A/P	0.9348	likely_pathogenic	0.9239	pathogenic	-0.307	Destabilizing	1.0	D	0.831	deleterious	D	0.523114337	None	None	I
A/Q	0.6704	likely_pathogenic	0.6708	pathogenic	-0.596	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
A/R	0.7608	likely_pathogenic	0.7605	pathogenic	-0.079	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
A/S	0.1792	likely_benign	0.1839	benign	-0.441	Destabilizing	1.0	D	0.637	neutral	N	0.47042096	None	None	I
A/T	0.2471	likely_benign	0.2476	benign	-0.536	Destabilizing	1.0	D	0.799	deleterious	N	0.487866878	None	None	I
A/V	0.1561	likely_benign	0.1589	benign	-0.307	Destabilizing	1.0	D	0.739	prob.delet.	N	0.433940195	None	None	I
A/W	0.933	likely_pathogenic	0.9306	pathogenic	-1.038	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	I
A/Y	0.7847	likely_pathogenic	0.7863	pathogenic	-0.702	Destabilizing	1.0	D	0.888	deleterious	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.