TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17096	51511;51512;51513	chr2:178610240;178610239;178610238	chr2:179474967;179474966;179474965
N2AB	15455	46588;46589;46590	chr2:178610240;178610239;178610238	chr2:179474967;179474966;179474965
N2A	14528	43807;43808;43809	chr2:178610240;178610239;178610238	chr2:179474967;179474966;179474965
N2B	8031	24316;24317;24318	chr2:178610240;178610239;178610238	chr2:179474967;179474966;179474965
Novex-1	8156	24691;24692;24693	chr2:178610240;178610239;178610238	chr2:179474967;179474966;179474965
Novex-2	8223	24892;24893;24894	chr2:178610240;178610239;178610238	chr2:179474967;179474966;179474965
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: Fn3-12
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.4623
• 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	rs772628026	-0.24	0.98	N	0.507	0.38	0.598305510223	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
P/L	rs772628026	-0.24	0.98	N	0.507	0.38	0.598305510223	gnomAD-4.0.0	6.16046E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.0983E-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	0.1824	likely_benign	0.2134	benign	-1.003	Destabilizing	0.961	D	0.399	neutral	N	0.468090054	None	None	N
P/C	0.8592	likely_pathogenic	0.8786	pathogenic	-0.728	Destabilizing	1.0	D	0.63	neutral	None	None	None	None	N
P/D	0.8693	likely_pathogenic	0.8742	pathogenic	-0.886	Destabilizing	0.942	D	0.399	neutral	None	None	None	None	N
P/E	0.748	likely_pathogenic	0.7537	pathogenic	-0.956	Destabilizing	0.97	D	0.409	neutral	None	None	None	None	N
P/F	0.945	likely_pathogenic	0.9548	pathogenic	-0.92	Destabilizing	0.999	D	0.599	neutral	None	None	None	None	N
P/G	0.638	likely_pathogenic	0.6783	pathogenic	-1.222	Destabilizing	0.97	D	0.427	neutral	None	None	None	None	N
P/H	0.6042	likely_pathogenic	0.6336	pathogenic	-0.695	Destabilizing	0.996	D	0.584	neutral	None	None	None	None	N
P/I	0.8322	likely_pathogenic	0.8574	pathogenic	-0.54	Destabilizing	0.999	D	0.6	neutral	None	None	None	None	N
P/K	0.8017	likely_pathogenic	0.8147	pathogenic	-0.946	Destabilizing	0.304	N	0.307	neutral	None	None	None	None	N
P/L	0.4728	ambiguous	0.5299	ambiguous	-0.54	Destabilizing	0.98	D	0.507	neutral	N	0.485926453	None	None	N
P/M	0.7643	likely_pathogenic	0.8035	pathogenic	-0.443	Destabilizing	1.0	D	0.578	neutral	None	None	None	None	N
P/N	0.6574	likely_pathogenic	0.6979	pathogenic	-0.671	Destabilizing	0.155	N	0.295	neutral	None	None	None	None	N
P/Q	0.4917	ambiguous	0.5094	ambiguous	-0.916	Destabilizing	0.989	D	0.491	neutral	N	0.484982304	None	None	N
P/R	0.6681	likely_pathogenic	0.659	pathogenic	-0.322	Destabilizing	0.925	D	0.493	neutral	N	0.476901538	None	None	N
P/S	0.3118	likely_benign	0.3582	ambiguous	-1.072	Destabilizing	0.961	D	0.397	neutral	N	0.49371643	None	None	N
P/T	0.319	likely_benign	0.3641	ambiguous	-1.044	Destabilizing	0.961	D	0.407	neutral	N	0.457448986	None	None	N
P/V	0.6347	likely_pathogenic	0.6771	pathogenic	-0.659	Destabilizing	0.996	D	0.485	neutral	None	None	None	None	N
P/W	0.9679	likely_pathogenic	0.9701	pathogenic	-1.03	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
P/Y	0.9226	likely_pathogenic	0.9327	pathogenic	-0.764	Destabilizing	0.999	D	0.603	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.