TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30940	93043;93044;93045	chr2:178548808;178548807;178548806	chr2:179413535;179413534;179413533
N2AB	29299	88120;88121;88122	chr2:178548808;178548807;178548806	chr2:179413535;179413534;179413533
N2A	28372	85339;85340;85341	chr2:178548808;178548807;178548806	chr2:179413535;179413534;179413533
N2B	21875	65848;65849;65850	chr2:178548808;178548807;178548806	chr2:179413535;179413534;179413533
Novex-1	22000	66223;66224;66225	chr2:178548808;178548807;178548806	chr2:179413535;179413534;179413533
Novex-2	22067	66424;66425;66426	chr2:178548808;178548807;178548806	chr2:179413535;179413534;179413533
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-150
• Domain position: 14
• Structural Position: 24
• Q(SASA): 0.2716
• 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/E	rs770455196	-0.928	1.0	D	0.879	0.86	0.881708220942	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
G/E	rs770455196	-0.928	1.0	D	0.879	0.86	0.881708220942	gnomAD-4.0.0	1.36946E-06	None	None	None	None	I	None	2.98811E-05	0	None	0	0	None	0	0	8.99462E-07	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	0.541	ambiguous	0.5307	ambiguous	-0.202	Destabilizing	1.0	D	0.783	deleterious	D	0.593180233	None	None	I
G/C	0.6942	likely_pathogenic	0.693	pathogenic	-0.784	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
G/D	0.6467	likely_pathogenic	0.6985	pathogenic	-0.68	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	I
G/E	0.7738	likely_pathogenic	0.7972	pathogenic	-0.858	Destabilizing	1.0	D	0.879	deleterious	D	0.585034828	None	None	I
G/F	0.9528	likely_pathogenic	0.9546	pathogenic	-1.058	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
G/H	0.8237	likely_pathogenic	0.8459	pathogenic	-0.42	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	I
G/I	0.9605	likely_pathogenic	0.961	pathogenic	-0.425	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
G/K	0.843	likely_pathogenic	0.8605	pathogenic	-0.663	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
G/L	0.9151	likely_pathogenic	0.9189	pathogenic	-0.425	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
G/M	0.9175	likely_pathogenic	0.9187	pathogenic	-0.369	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	I
G/N	0.5962	likely_pathogenic	0.6379	pathogenic	-0.31	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
G/P	0.9917	likely_pathogenic	0.9916	pathogenic	-0.32	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	I
G/Q	0.7564	likely_pathogenic	0.7816	pathogenic	-0.643	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	I
G/R	0.7312	likely_pathogenic	0.75	pathogenic	-0.187	Destabilizing	1.0	D	0.891	deleterious	D	0.609633563	None	None	I
G/S	0.2966	likely_benign	0.3046	benign	-0.413	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
G/T	0.7082	likely_pathogenic	0.716	pathogenic	-0.531	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	I
G/V	0.9088	likely_pathogenic	0.9051	pathogenic	-0.32	Destabilizing	1.0	D	0.849	deleterious	D	0.635141314	None	None	I
G/W	0.925	likely_pathogenic	0.9326	pathogenic	-1.185	Destabilizing	1.0	D	0.878	deleterious	D	0.635343118	None	None	I
G/Y	0.9129	likely_pathogenic	0.9204	pathogenic	-0.832	Destabilizing	1.0	D	0.855	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.