TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32181	96766;96767;96768	chr2:178543432;178543431;178543430	chr2:179408159;179408158;179408157
N2AB	30540	91843;91844;91845	chr2:178543432;178543431;178543430	chr2:179408159;179408158;179408157
N2A	29613	89062;89063;89064	chr2:178543432;178543431;178543430	chr2:179408159;179408158;179408157
N2B	23116	69571;69572;69573	chr2:178543432;178543431;178543430	chr2:179408159;179408158;179408157
Novex-1	23241	69946;69947;69948	chr2:178543432;178543431;178543430	chr2:179408159;179408158;179408157
Novex-2	23308	70147;70148;70149	chr2:178543432;178543431;178543430	chr2:179408159;179408158;179408157
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: Fn3-122
• Domain position: 77
• Structural Position: 110
• Q(SASA): 0.1175
• 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/S	rs1695557905	None	0.998	N	0.771	0.391	0.287603790349	gnomAD-4.0.0	1.59143E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85843E-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	0.1717	likely_benign	0.159	benign	-2.578	Highly Destabilizing	0.767	D	0.523	neutral	N	0.272441448	None	None	N
P/C	0.9013	likely_pathogenic	0.8828	pathogenic	-2.25	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
P/D	0.9975	likely_pathogenic	0.9973	pathogenic	-3.141	Highly Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
P/E	0.9931	likely_pathogenic	0.9908	pathogenic	-2.919	Highly Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
P/F	0.998	likely_pathogenic	0.996	pathogenic	-1.048	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
P/G	0.6956	likely_pathogenic	0.6828	pathogenic	-3.008	Highly Destabilizing	0.997	D	0.787	deleterious	None	None	None	None	N
P/H	0.9905	likely_pathogenic	0.985	pathogenic	-2.404	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
P/I	0.9879	likely_pathogenic	0.9778	pathogenic	-1.326	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
P/K	0.9973	likely_pathogenic	0.9962	pathogenic	-1.955	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
P/L	0.9173	likely_pathogenic	0.8655	pathogenic	-1.326	Destabilizing	0.999	D	0.813	deleterious	N	0.484558229	None	None	N
P/M	0.9802	likely_pathogenic	0.9683	pathogenic	-1.731	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
P/N	0.9904	likely_pathogenic	0.9879	pathogenic	-2.387	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
P/Q	0.9778	likely_pathogenic	0.968	pathogenic	-2.142	Highly Destabilizing	1.0	D	0.831	deleterious	N	0.485771737	None	None	N
P/R	0.988	likely_pathogenic	0.9824	pathogenic	-1.811	Destabilizing	0.999	D	0.819	deleterious	N	0.485771737	None	None	N
P/S	0.6017	likely_pathogenic	0.5808	pathogenic	-2.855	Highly Destabilizing	0.998	D	0.771	deleterious	N	0.394803017	None	None	N
P/T	0.7823	likely_pathogenic	0.752	pathogenic	-2.528	Highly Destabilizing	0.999	D	0.776	deleterious	N	0.464142885	None	None	N
P/V	0.9386	likely_pathogenic	0.9071	pathogenic	-1.73	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
P/W	0.9992	likely_pathogenic	0.9985	pathogenic	-1.466	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
P/Y	0.9979	likely_pathogenic	0.9961	pathogenic	-1.406	Destabilizing	1.0	D	0.871	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.