TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22011	66256;66257;66258	chr2:178582425;178582424;178582423	chr2:179447152;179447151;179447150
N2AB	20370	61333;61334;61335	chr2:178582425;178582424;178582423	chr2:179447152;179447151;179447150
N2A	19443	58552;58553;58554	chr2:178582425;178582424;178582423	chr2:179447152;179447151;179447150
N2B	12946	39061;39062;39063	chr2:178582425;178582424;178582423	chr2:179447152;179447151;179447150
Novex-1	13071	39436;39437;39438	chr2:178582425;178582424;178582423	chr2:179447152;179447151;179447150
Novex-2	13138	39637;39638;39639	chr2:178582425;178582424;178582423	chr2:179447152;179447151;179447150
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: Fn3-47
• Domain position: 56
• Structural Position: 83
• Q(SASA): 0.6077
• 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/H	None	None	0.002	N	0.229	0.259	0.24896430686	gnomAD-4.0.0	1.20034E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05
P/S	rs758402332	-0.667	0.351	N	0.306	0.279	0.233150807113	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
P/S	rs758402332	-0.667	0.351	N	0.306	0.279	0.233150807113	gnomAD-4.0.0	3.18631E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72246E-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	0.1004	likely_benign	0.0885	benign	-0.818	Destabilizing	0.183	N	0.287	neutral	N	0.471477076	None	None	N
P/C	0.6344	likely_pathogenic	0.5536	ambiguous	-0.823	Destabilizing	0.983	D	0.327	neutral	None	None	None	None	N
P/D	0.5089	ambiguous	0.506	ambiguous	-0.329	Destabilizing	0.002	N	0.151	neutral	None	None	None	None	N
P/E	0.3169	likely_benign	0.308	benign	-0.388	Destabilizing	0.129	N	0.294	neutral	None	None	None	None	N
P/F	0.6682	likely_pathogenic	0.6113	pathogenic	-0.724	Destabilizing	0.557	D	0.363	neutral	None	None	None	None	N
P/G	0.3238	likely_benign	0.2908	benign	-1.027	Destabilizing	0.418	N	0.313	neutral	None	None	None	None	N
P/H	0.2768	likely_benign	0.2404	benign	-0.427	Destabilizing	0.002	N	0.229	neutral	N	0.45341139	None	None	N
P/I	0.4468	ambiguous	0.3708	ambiguous	-0.389	Destabilizing	0.557	D	0.39	neutral	None	None	None	None	N
P/K	0.2979	likely_benign	0.2827	benign	-0.688	Destabilizing	0.264	N	0.311	neutral	None	None	None	None	N
P/L	0.1797	likely_benign	0.1502	benign	-0.389	Destabilizing	0.002	N	0.242	neutral	N	0.500165187	None	None	N
P/M	0.385	ambiguous	0.3187	benign	-0.483	Destabilizing	0.716	D	0.319	neutral	None	None	None	None	N
P/N	0.35	ambiguous	0.3133	benign	-0.54	Destabilizing	0.418	N	0.324	neutral	None	None	None	None	N
P/Q	0.1732	likely_benign	0.1482	benign	-0.717	Destabilizing	0.01	N	0.143	neutral	None	None	None	None	N
P/R	0.2435	likely_benign	0.2226	benign	-0.172	Destabilizing	0.213	N	0.355	neutral	N	0.432670758	None	None	N
P/S	0.1499	likely_benign	0.1317	benign	-1.001	Destabilizing	0.351	N	0.306	neutral	N	0.440018018	None	None	N
P/T	0.1285	likely_benign	0.1128	benign	-0.948	Destabilizing	0.351	N	0.311	neutral	N	0.422104261	None	None	N
P/V	0.2923	likely_benign	0.243	benign	-0.496	Destabilizing	0.264	N	0.319	neutral	None	None	None	None	N
P/W	0.8001	likely_pathogenic	0.7551	pathogenic	-0.817	Destabilizing	0.983	D	0.342	neutral	None	None	None	None	N
P/Y	0.6124	likely_pathogenic	0.5525	ambiguous	-0.53	Destabilizing	0.716	D	0.376	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.