TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17015	51268;51269;51270	chr2:178611086;178611085;178611084	chr2:179475813;179475812;179475811
N2AB	15374	46345;46346;46347	chr2:178611086;178611085;178611084	chr2:179475813;179475812;179475811
N2A	14447	43564;43565;43566	chr2:178611086;178611085;178611084	chr2:179475813;179475812;179475811
N2B	7950	24073;24074;24075	chr2:178611086;178611085;178611084	chr2:179475813;179475812;179475811
Novex-1	8075	24448;24449;24450	chr2:178611086;178611085;178611084	chr2:179475813;179475812;179475811
Novex-2	8142	24649;24650;24651	chr2:178611086;178611085;178611084	chr2:179475813;179475812;179475811
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-111
• Domain position: 61
• Structural Position: 141
• Q(SASA): 0.217
• 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	None	None	0.001	N	0.29	0.162	0.542896531885	gnomAD-4.0.0	1.59324E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86218E-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	0.0861	likely_benign	0.0978	benign	-1.035	Destabilizing	None	N	0.181	neutral	N	0.506825913	None	None	N
P/C	0.4922	ambiguous	0.5512	ambiguous	-0.832	Destabilizing	0.667	D	0.513	neutral	None	None	None	None	N
P/D	0.2949	likely_benign	0.3546	ambiguous	-0.903	Destabilizing	0.001	N	0.225	neutral	None	None	None	None	N
P/E	0.2041	likely_benign	0.2361	benign	-0.989	Destabilizing	0.055	N	0.434	neutral	None	None	None	None	N
P/F	0.4054	ambiguous	0.5055	ambiguous	-1.063	Destabilizing	0.497	N	0.557	neutral	None	None	None	None	N
P/G	0.2463	likely_benign	0.273	benign	-1.241	Destabilizing	0.055	N	0.43	neutral	None	None	None	None	N
P/H	0.1954	likely_benign	0.236	benign	-0.733	Destabilizing	0.602	D	0.497	neutral	N	0.50892316	None	None	N
P/I	0.2378	likely_benign	0.3104	benign	-0.613	Destabilizing	0.001	N	0.379	neutral	None	None	None	None	N
P/K	0.2483	likely_benign	0.2965	benign	-0.807	Destabilizing	0.055	N	0.434	neutral	None	None	None	None	N
P/L	0.1051	likely_benign	0.1288	benign	-0.613	Destabilizing	0.001	N	0.29	neutral	N	0.466192217	None	None	N
P/M	0.2376	likely_benign	0.2894	benign	-0.443	Destabilizing	0.497	N	0.514	neutral	None	None	None	None	N
P/N	0.2262	likely_benign	0.2813	benign	-0.531	Destabilizing	0.22	N	0.478	neutral	None	None	None	None	N
P/Q	0.1425	likely_benign	0.167	benign	-0.831	Destabilizing	0.22	N	0.502	neutral	None	None	None	None	N
P/R	0.2021	likely_benign	0.2362	benign	-0.206	Destabilizing	0.001	N	0.357	neutral	N	0.476160009	None	None	N
P/S	0.1096	likely_benign	0.1307	benign	-0.966	Destabilizing	0.003	N	0.208	neutral	N	0.482961137	None	None	N
P/T	0.0875	likely_benign	0.1043	benign	-0.954	Destabilizing	0.001	N	0.165	neutral	N	0.493884989	None	None	N
P/V	0.1828	likely_benign	0.2172	benign	-0.718	Destabilizing	0.055	N	0.432	neutral	None	None	None	None	N
P/W	0.5806	likely_pathogenic	0.6348	pathogenic	-1.118	Destabilizing	0.958	D	0.529	neutral	None	None	None	None	N
P/Y	0.4158	ambiguous	0.4791	ambiguous	-0.839	Destabilizing	0.667	D	0.545	neutral	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.