TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32133	96622;96623;96624	chr2:178543576;178543575;178543574	chr2:179408303;179408302;179408301
N2AB	30492	91699;91700;91701	chr2:178543576;178543575;178543574	chr2:179408303;179408302;179408301
N2A	29565	88918;88919;88920	chr2:178543576;178543575;178543574	chr2:179408303;179408302;179408301
N2B	23068	69427;69428;69429	chr2:178543576;178543575;178543574	chr2:179408303;179408302;179408301
Novex-1	23193	69802;69803;69804	chr2:178543576;178543575;178543574	chr2:179408303;179408302;179408301
Novex-2	23260	70003;70004;70005	chr2:178543576;178543575;178543574	chr2:179408303;179408302;179408301
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: Fn3-122
• Domain position: 29
• Structural Position: 31
• Q(SASA): 0.326
• 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	rs1454628830	None	1.0	N	0.83	0.588	0.40017627803	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
G/D	rs1454628830	None	1.0	N	0.83	0.588	0.40017627803	gnomAD-4.0.0	6.57099E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.46998E-05	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	0.9629	likely_pathogenic	0.9606	pathogenic	-0.491	Destabilizing	1.0	D	0.725	prob.delet.	N	0.521264231	None	None	I
G/C	0.9898	likely_pathogenic	0.9878	pathogenic	-0.777	Destabilizing	1.0	D	0.792	deleterious	D	0.533887984	None	None	I
G/D	0.9982	likely_pathogenic	0.9978	pathogenic	-0.78	Destabilizing	1.0	D	0.83	deleterious	N	0.512995344	None	None	I
G/E	0.9987	likely_pathogenic	0.9984	pathogenic	-0.918	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	I
G/F	0.999	likely_pathogenic	0.9988	pathogenic	-1.112	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
G/H	0.9991	likely_pathogenic	0.9988	pathogenic	-0.923	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
G/I	0.9987	likely_pathogenic	0.9986	pathogenic	-0.443	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
G/K	0.9988	likely_pathogenic	0.9985	pathogenic	-0.997	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
G/L	0.9983	likely_pathogenic	0.998	pathogenic	-0.443	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
G/M	0.9992	likely_pathogenic	0.9991	pathogenic	-0.348	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
G/N	0.998	likely_pathogenic	0.9977	pathogenic	-0.554	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
G/P	0.9997	likely_pathogenic	0.9997	pathogenic	-0.422	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
G/Q	0.9986	likely_pathogenic	0.9982	pathogenic	-0.836	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
G/R	0.9951	likely_pathogenic	0.9932	pathogenic	-0.567	Destabilizing	1.0	D	0.831	deleterious	N	0.496158537	None	None	I
G/S	0.9576	likely_pathogenic	0.9498	pathogenic	-0.728	Destabilizing	1.0	D	0.799	deleterious	N	0.504855043	None	None	I
G/T	0.9948	likely_pathogenic	0.9947	pathogenic	-0.797	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
G/V	0.9971	likely_pathogenic	0.9967	pathogenic	-0.422	Destabilizing	1.0	D	0.82	deleterious	D	0.5220247	None	None	I
G/W	0.9978	likely_pathogenic	0.9971	pathogenic	-1.326	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
G/Y	0.9985	likely_pathogenic	0.9983	pathogenic	-0.961	Destabilizing	1.0	D	0.787	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.