TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23370	70333;70334;70335	chr2:178576024;178576023;178576022	chr2:179440751;179440750;179440749
N2AB	21729	65410;65411;65412	chr2:178576024;178576023;178576022	chr2:179440751;179440750;179440749
N2A	20802	62629;62630;62631	chr2:178576024;178576023;178576022	chr2:179440751;179440750;179440749
N2B	14305	43138;43139;43140	chr2:178576024;178576023;178576022	chr2:179440751;179440750;179440749
Novex-1	14430	43513;43514;43515	chr2:178576024;178576023;178576022	chr2:179440751;179440750;179440749
Novex-2	14497	43714;43715;43716	chr2:178576024;178576023;178576022	chr2:179440751;179440750;179440749
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: Ig-129
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.2971
• 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	rs1372713604	None	1.0	D	0.837	0.82	0.647389606501	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
G/D	rs1372713604	None	1.0	D	0.837	0.82	0.647389606501	gnomAD-4.0.0	1.23988E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.69573E-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
G/A	0.8137	likely_pathogenic	0.8658	pathogenic	-0.297	Destabilizing	1.0	D	0.756	deleterious	D	0.555107025	None	None	I
G/C	0.9769	likely_pathogenic	0.9865	pathogenic	-0.752	Destabilizing	1.0	D	0.715	prob.delet.	D	0.622827664	None	None	I
G/D	0.9948	likely_pathogenic	0.9965	pathogenic	-0.899	Destabilizing	1.0	D	0.837	deleterious	D	0.621616838	None	None	I
G/E	0.9968	likely_pathogenic	0.9977	pathogenic	-1.051	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
G/F	0.9979	likely_pathogenic	0.9985	pathogenic	-0.991	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
G/H	0.9991	likely_pathogenic	0.9995	pathogenic	-0.699	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
G/I	0.9967	likely_pathogenic	0.9979	pathogenic	-0.373	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
G/K	0.9991	likely_pathogenic	0.9994	pathogenic	-1.051	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
G/L	0.9966	likely_pathogenic	0.9977	pathogenic	-0.373	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
G/M	0.9981	likely_pathogenic	0.9988	pathogenic	-0.451	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
G/N	0.9972	likely_pathogenic	0.9983	pathogenic	-0.565	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
G/P	0.9993	likely_pathogenic	0.9996	pathogenic	-0.314	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
G/Q	0.9984	likely_pathogenic	0.999	pathogenic	-0.853	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
G/R	0.9972	likely_pathogenic	0.9981	pathogenic	-0.591	Destabilizing	1.0	D	0.81	deleterious	D	0.622424056	None	None	I
G/S	0.9243	likely_pathogenic	0.9566	pathogenic	-0.643	Destabilizing	1.0	D	0.82	deleterious	D	0.605799282	None	None	I
G/T	0.9907	likely_pathogenic	0.9943	pathogenic	-0.738	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
G/V	0.9901	likely_pathogenic	0.9932	pathogenic	-0.314	Destabilizing	1.0	D	0.793	deleterious	D	0.622424056	None	None	I
G/W	0.9966	likely_pathogenic	0.9978	pathogenic	-1.199	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
G/Y	0.9971	likely_pathogenic	0.9982	pathogenic	-0.849	Destabilizing	1.0	D	0.76	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.