TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17397	52414;52415;52416	chr2:178608822;178608821;178608820	chr2:179473549;179473548;179473547
N2AB	15756	47491;47492;47493	chr2:178608822;178608821;178608820	chr2:179473549;179473548;179473547
N2A	14829	44710;44711;44712	chr2:178608822;178608821;178608820	chr2:179473549;179473548;179473547
N2B	8332	25219;25220;25221	chr2:178608822;178608821;178608820	chr2:179473549;179473548;179473547
Novex-1	8457	25594;25595;25596	chr2:178608822;178608821;178608820	chr2:179473549;179473548;179473547
Novex-2	8524	25795;25796;25797	chr2:178608822;178608821;178608820	chr2:179473549;179473548;179473547
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-14
• Domain position: 29
• Structural Position: 31
• Q(SASA): 0.2963
• 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
G/D	rs2055561994	None	1.0	D	0.843	0.63	0.425851741357	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
G/D	rs2055561994	None	1.0	D	0.843	0.63	0.425851741357	gnomAD-4.0.0	6.58111E-06	None	None	None	None	I	None	2.41488E-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
G/A	0.9767	likely_pathogenic	0.9822	pathogenic	-0.227	Destabilizing	1.0	D	0.726	prob.delet.	N	0.516985044	None	None	I
G/C	0.9935	likely_pathogenic	0.9953	pathogenic	-0.772	Destabilizing	1.0	D	0.8	deleterious	D	0.544750537	None	None	I
G/D	0.9985	likely_pathogenic	0.9988	pathogenic	-0.348	Destabilizing	1.0	D	0.843	deleterious	D	0.541962152	None	None	I
G/E	0.9989	likely_pathogenic	0.9992	pathogenic	-0.51	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	I
G/F	0.999	likely_pathogenic	0.9994	pathogenic	-1.023	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
G/H	0.9992	likely_pathogenic	0.9994	pathogenic	-0.54	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
G/I	0.9992	likely_pathogenic	0.9995	pathogenic	-0.352	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
G/K	0.9988	likely_pathogenic	0.9991	pathogenic	-0.584	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	I
G/L	0.9988	likely_pathogenic	0.9992	pathogenic	-0.352	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
G/M	0.9993	likely_pathogenic	0.9996	pathogenic	-0.3	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
G/N	0.9988	likely_pathogenic	0.999	pathogenic	-0.22	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
G/P	0.9997	likely_pathogenic	0.9999	pathogenic	-0.277	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
G/Q	0.9987	likely_pathogenic	0.999	pathogenic	-0.51	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
G/R	0.9956	likely_pathogenic	0.9964	pathogenic	-0.205	Destabilizing	1.0	D	0.845	deleterious	N	0.498627299	None	None	I
G/S	0.9798	likely_pathogenic	0.9828	pathogenic	-0.405	Destabilizing	1.0	D	0.806	deleterious	N	0.506007132	None	None	I
G/T	0.9969	likely_pathogenic	0.998	pathogenic	-0.493	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	I
G/V	0.9983	likely_pathogenic	0.999	pathogenic	-0.277	Destabilizing	1.0	D	0.821	deleterious	D	0.526139303	None	None	I
G/W	0.998	likely_pathogenic	0.9987	pathogenic	-1.176	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
G/Y	0.9989	likely_pathogenic	0.9992	pathogenic	-0.798	Destabilizing	1.0	D	0.791	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.