TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23854	71785;71786;71787	chr2:178574572;178574571;178574570	chr2:179439299;179439298;179439297
N2AB	22213	66862;66863;66864	chr2:178574572;178574571;178574570	chr2:179439299;179439298;179439297
N2A	21286	64081;64082;64083	chr2:178574572;178574571;178574570	chr2:179439299;179439298;179439297
N2B	14789	44590;44591;44592	chr2:178574572;178574571;178574570	chr2:179439299;179439298;179439297
Novex-1	14914	44965;44966;44967	chr2:178574572;178574571;178574570	chr2:179439299;179439298;179439297
Novex-2	14981	45166;45167;45168	chr2:178574572;178574571;178574570	chr2:179439299;179439298;179439297
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: Fn3-61
• Domain position: 29
• Structural Position: 31
• Q(SASA): 0.4316
• 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/V	rs1472507638	-0.245	1.0	D	0.844	0.672	0.614419055545	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
G/V	rs1472507638	-0.245	1.0	D	0.844	0.672	0.614419055545	gnomAD-4.0.0	1.5918E-06	None	None	None	None	I	None	0	2.28666E-05	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	0.8582	likely_pathogenic	0.8793	pathogenic	-0.234	Destabilizing	1.0	D	0.739	prob.delet.	N	0.515628691	None	None	I
G/C	0.9426	likely_pathogenic	0.9517	pathogenic	-0.848	Destabilizing	1.0	D	0.815	deleterious	D	0.55475049	None	None	I
G/D	0.9826	likely_pathogenic	0.9849	pathogenic	-0.612	Destabilizing	1.0	D	0.83	deleterious	N	0.514868222	None	None	I
G/E	0.988	likely_pathogenic	0.9898	pathogenic	-0.784	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	I
G/F	0.9944	likely_pathogenic	0.9951	pathogenic	-1.064	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	I
G/H	0.9902	likely_pathogenic	0.9917	pathogenic	-0.452	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
G/I	0.9937	likely_pathogenic	0.9951	pathogenic	-0.445	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
G/K	0.9927	likely_pathogenic	0.9931	pathogenic	-0.655	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	I
G/L	0.9921	likely_pathogenic	0.993	pathogenic	-0.445	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	I
G/M	0.9942	likely_pathogenic	0.995	pathogenic	-0.418	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
G/N	0.9694	likely_pathogenic	0.9744	pathogenic	-0.341	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
G/P	0.9991	likely_pathogenic	0.9992	pathogenic	-0.344	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I
G/Q	0.9857	likely_pathogenic	0.9877	pathogenic	-0.654	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
G/R	0.9734	likely_pathogenic	0.9756	pathogenic	-0.204	Destabilizing	1.0	D	0.861	deleterious	N	0.51347587	None	None	I
G/S	0.7769	likely_pathogenic	0.7943	pathogenic	-0.459	Destabilizing	1.0	D	0.808	deleterious	N	0.516260574	None	None	I
G/T	0.9741	likely_pathogenic	0.9777	pathogenic	-0.566	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	I
G/V	0.9875	likely_pathogenic	0.9894	pathogenic	-0.344	Destabilizing	1.0	D	0.844	deleterious	D	0.542976111	None	None	I
G/W	0.9883	likely_pathogenic	0.9906	pathogenic	-1.19	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
G/Y	0.9896	likely_pathogenic	0.9907	pathogenic	-0.838	Destabilizing	1.0	D	0.819	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.