TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31309	94150;94151;94152	chr2:178547701;178547700;178547699	chr2:179412428;179412427;179412426
N2AB	29668	89227;89228;89229	chr2:178547701;178547700;178547699	chr2:179412428;179412427;179412426
N2A	28741	86446;86447;86448	chr2:178547701;178547700;178547699	chr2:179412428;179412427;179412426
N2B	22244	66955;66956;66957	chr2:178547701;178547700;178547699	chr2:179412428;179412427;179412426
Novex-1	22369	67330;67331;67332	chr2:178547701;178547700;178547699	chr2:179412428;179412427;179412426
Novex-2	22436	67531;67532;67533	chr2:178547701;178547700;178547699	chr2:179412428;179412427;179412426
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-116
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.1016
• Predicted PPI site: N

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
P/L	rs1697796089	None	1.0	D	0.847	0.675	0.871878411553	gnomAD-4.0.0	1.59106E-06	None	None	None	None	N	None	0	2.28655E-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
P/A	0.8872	likely_pathogenic	0.8113	pathogenic	-1.307	Destabilizing	0.999	D	0.83	deleterious	D	0.613323171	None	None	N
P/C	0.9865	likely_pathogenic	0.9745	pathogenic	-2.066	Highly Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
P/D	0.9978	likely_pathogenic	0.9964	pathogenic	-2.982	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
P/E	0.9952	likely_pathogenic	0.992	pathogenic	-2.946	Highly Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
P/F	0.9994	likely_pathogenic	0.9989	pathogenic	-1.147	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
P/G	0.9903	likely_pathogenic	0.9822	pathogenic	-1.576	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
P/H	0.9955	likely_pathogenic	0.9906	pathogenic	-1.0	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
P/I	0.9922	likely_pathogenic	0.9865	pathogenic	-0.644	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
P/K	0.9977	likely_pathogenic	0.9954	pathogenic	-1.376	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
P/L	0.9711	likely_pathogenic	0.954	pathogenic	-0.644	Destabilizing	1.0	D	0.847	deleterious	D	0.61372678	None	None	N
P/M	0.996	likely_pathogenic	0.9923	pathogenic	-0.961	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
P/N	0.9975	likely_pathogenic	0.9947	pathogenic	-1.666	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
P/Q	0.994	likely_pathogenic	0.9879	pathogenic	-1.892	Destabilizing	1.0	D	0.865	deleterious	D	0.655718221	None	None	N
P/R	0.9914	likely_pathogenic	0.9849	pathogenic	-0.884	Destabilizing	1.0	D	0.849	deleterious	D	0.639264891	None	None	N
P/S	0.9811	likely_pathogenic	0.9615	pathogenic	-1.989	Destabilizing	1.0	D	0.804	deleterious	D	0.655314613	None	None	N
P/T	0.9753	likely_pathogenic	0.9505	pathogenic	-1.855	Destabilizing	1.0	D	0.815	deleterious	D	0.639264891	None	None	N
P/V	0.9792	likely_pathogenic	0.9616	pathogenic	-0.838	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
P/W	0.9996	likely_pathogenic	0.9993	pathogenic	-1.396	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
P/Y	0.9992	likely_pathogenic	0.9983	pathogenic	-1.02	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N

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.