TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7515	22768;22769;22770	chr2:178722120;178722119;178722118	chr2:179586847;179586846;179586845
N2AB	7198	21817;21818;21819	chr2:178722120;178722119;178722118	chr2:179586847;179586846;179586845
N2A	6271	19036;19037;19038	chr2:178722120;178722119;178722118	chr2:179586847;179586846;179586845
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: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-60
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.1531
• 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/R	None	None	1.0	D	0.889	0.577	0.895621291542	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-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
P/A	0.7382	likely_pathogenic	0.7511	pathogenic	-1.819	Destabilizing	1.0	D	0.835	deleterious	D	0.629549721	None	None	N
P/C	0.9841	likely_pathogenic	0.9827	pathogenic	-1.408	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
P/D	0.9986	likely_pathogenic	0.9984	pathogenic	-2.304	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
P/E	0.9964	likely_pathogenic	0.9958	pathogenic	-2.256	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
P/F	0.997	likely_pathogenic	0.9967	pathogenic	-1.376	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
P/G	0.9848	likely_pathogenic	0.9831	pathogenic	-2.182	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
P/H	0.9927	likely_pathogenic	0.9919	pathogenic	-1.757	Destabilizing	1.0	D	0.854	deleterious	D	0.655693245	None	None	N
P/I	0.9337	likely_pathogenic	0.9384	pathogenic	-0.881	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
P/K	0.9976	likely_pathogenic	0.9973	pathogenic	-1.444	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
P/L	0.8721	likely_pathogenic	0.8816	pathogenic	-0.881	Destabilizing	1.0	D	0.883	deleterious	D	0.613701804	None	None	N
P/M	0.9858	likely_pathogenic	0.9864	pathogenic	-0.764	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
P/N	0.9962	likely_pathogenic	0.996	pathogenic	-1.408	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
P/Q	0.9908	likely_pathogenic	0.9901	pathogenic	-1.555	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/R	0.9861	likely_pathogenic	0.9848	pathogenic	-0.982	Destabilizing	1.0	D	0.889	deleterious	D	0.655693245	None	None	N
P/S	0.9612	likely_pathogenic	0.9622	pathogenic	-1.918	Destabilizing	1.0	D	0.902	deleterious	D	0.639038111	None	None	N
P/T	0.9446	likely_pathogenic	0.9422	pathogenic	-1.763	Destabilizing	1.0	D	0.899	deleterious	D	0.655491441	None	None	N
P/V	0.8678	likely_pathogenic	0.8739	pathogenic	-1.163	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
P/W	0.9991	likely_pathogenic	0.9991	pathogenic	-1.668	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
P/Y	0.998	likely_pathogenic	0.9976	pathogenic	-1.361	Destabilizing	1.0	D	0.885	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.