TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18722	56389;56390;56391	chr2:178599737;178599736;178599735	chr2:179464464;179464463;179464462
N2AB	17081	51466;51467;51468	chr2:178599737;178599736;178599735	chr2:179464464;179464463;179464462
N2A	16154	48685;48686;48687	chr2:178599737;178599736;178599735	chr2:179464464;179464463;179464462
N2B	9657	29194;29195;29196	chr2:178599737;178599736;178599735	chr2:179464464;179464463;179464462
Novex-1	9782	29569;29570;29571	chr2:178599737;178599736;178599735	chr2:179464464;179464463;179464462
Novex-2	9849	29770;29771;29772	chr2:178599737;178599736;178599735	chr2:179464464;179464463;179464462
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-116
• Domain position: 35
• Structural Position: 52
• Q(SASA): 0.2752
• 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	rs1480758213	-0.477	0.007	N	0.309	0.146	0.413241256734	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	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	0.0744	likely_benign	0.0744	benign	-1.393	Destabilizing	0.012	N	0.181	neutral	N	0.449011222	None	None	N
P/C	0.4299	ambiguous	0.3803	ambiguous	-0.842	Destabilizing	0.996	D	0.439	neutral	None	None	None	None	N
P/D	0.3129	likely_benign	0.2597	benign	-1.24	Destabilizing	0.742	D	0.339	neutral	None	None	None	None	N
P/E	0.2155	likely_benign	0.1923	benign	-1.268	Destabilizing	0.742	D	0.335	neutral	None	None	None	None	N
P/F	0.3543	ambiguous	0.3122	benign	-1.124	Destabilizing	0.91	D	0.436	neutral	None	None	None	None	N
P/G	0.2791	likely_benign	0.2479	benign	-1.687	Destabilizing	0.59	D	0.351	neutral	None	None	None	None	N
P/H	0.1749	likely_benign	0.1432	benign	-1.273	Destabilizing	0.994	D	0.399	neutral	N	0.475544462	None	None	N
P/I	0.2279	likely_benign	0.2068	benign	-0.694	Destabilizing	0.59	D	0.37	neutral	None	None	None	None	N
P/K	0.2392	likely_benign	0.2016	benign	-1.196	Destabilizing	0.742	D	0.323	neutral	None	None	None	None	N
P/L	0.1056	likely_benign	0.0954	benign	-0.694	Destabilizing	0.007	N	0.309	neutral	N	0.463249955	None	None	N
P/M	0.2369	likely_benign	0.214	benign	-0.462	Destabilizing	0.91	D	0.398	neutral	None	None	None	None	N
P/N	0.2546	likely_benign	0.2045	benign	-0.878	Destabilizing	0.91	D	0.389	neutral	None	None	None	None	N
P/Q	0.1379	likely_benign	0.1232	benign	-1.085	Destabilizing	0.953	D	0.355	neutral	None	None	None	None	N
P/R	0.2012	likely_benign	0.1718	benign	-0.647	Destabilizing	0.884	D	0.391	neutral	N	0.459612217	None	None	N
P/S	0.103	likely_benign	0.0878	benign	-1.359	Destabilizing	0.012	N	0.177	neutral	N	0.418939031	None	None	N
P/T	0.0999	likely_benign	0.0935	benign	-1.284	Destabilizing	0.521	D	0.351	neutral	N	0.442797325	None	None	N
P/V	0.162	likely_benign	0.1525	benign	-0.891	Destabilizing	0.59	D	0.342	neutral	None	None	None	None	N
P/W	0.602	likely_pathogenic	0.525	ambiguous	-1.292	Destabilizing	0.996	D	0.522	neutral	None	None	None	None	N
P/Y	0.3514	ambiguous	0.3167	benign	-1.027	Destabilizing	0.953	D	0.437	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.