TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7809	23650;23651;23652	chr2:178720217;178720216;178720215	chr2:179584944;179584943;179584942
N2AB	7492	22699;22700;22701	chr2:178720217;178720216;178720215	chr2:179584944;179584943;179584942
N2A	6565	19918;19919;19920	chr2:178720217;178720216;178720215	chr2:179584944;179584943;179584942
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-63
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.2672
• 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/R	None	None	1.0	D	0.845	0.621	0.879840086486	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.3363	likely_benign	0.3424	ambiguous	-0.582	Destabilizing	0.996	D	0.691	prob.neutral	D	0.641470481	None	None	I
G/C	0.5376	ambiguous	0.5304	ambiguous	-1.041	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
G/D	0.3192	likely_benign	0.3171	benign	-0.796	Destabilizing	0.999	D	0.84	deleterious	None	None	None	None	I
G/E	0.3951	ambiguous	0.3846	ambiguous	-0.937	Destabilizing	0.991	D	0.596	neutral	D	0.598268213	None	None	I
G/F	0.852	likely_pathogenic	0.8541	pathogenic	-1.19	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	I
G/H	0.5806	likely_pathogenic	0.5869	pathogenic	-0.843	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I
G/I	0.8159	likely_pathogenic	0.8261	pathogenic	-0.577	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	I
G/K	0.6023	likely_pathogenic	0.5828	pathogenic	-1.013	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
G/L	0.7638	likely_pathogenic	0.7806	pathogenic	-0.577	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
G/M	0.8248	likely_pathogenic	0.8298	pathogenic	-0.496	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
G/N	0.3899	ambiguous	0.398	ambiguous	-0.701	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
G/P	0.9672	likely_pathogenic	0.9672	pathogenic	-0.543	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	I
G/Q	0.4997	ambiguous	0.497	ambiguous	-0.999	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
G/R	0.4127	ambiguous	0.4149	ambiguous	-0.557	Destabilizing	1.0	D	0.845	deleterious	D	0.620313137	None	None	I
G/S	0.1689	likely_benign	0.178	benign	-0.909	Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	I
G/T	0.4177	ambiguous	0.4265	ambiguous	-0.977	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
G/V	0.6811	likely_pathogenic	0.6941	pathogenic	-0.543	Destabilizing	1.0	D	0.833	deleterious	D	0.65789345	None	None	I
G/W	0.6616	likely_pathogenic	0.6504	pathogenic	-1.341	Destabilizing	1.0	D	0.843	deleterious	D	0.658095254	None	None	I
G/Y	0.7244	likely_pathogenic	0.7345	pathogenic	-0.996	Destabilizing	1.0	D	0.86	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.