TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7277	22054;22055;22056	chr2:178723178;178723177;178723176	chr2:179587905;179587904;179587903
N2AB	6960	21103;21104;21105	chr2:178723178;178723177;178723176	chr2:179587905;179587904;179587903
N2A	6033	18322;18323;18324	chr2:178723178;178723177;178723176	chr2:179587905;179587904;179587903
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-57
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.2749
• 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
N/D	rs758247611	-1.275	0.029	D	0.295	0.157	None	gnomAD-2.1.1	1.07E-05	None	None	None	None	N	None	1.24049E-04	0	None	0	0	None	0	None	0	0	0
N/D	rs758247611	-1.275	0.029	D	0.295	0.157	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	9.65E-05	0	0	0	0	None	0	0	0	0	0
N/D	rs758247611	-1.275	0.029	D	0.295	0.157	None	gnomAD-4.0.0	4.95831E-06	None	None	None	None	N	None	1.06815E-04	0	None	0	0	None	0	0	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
N/A	0.1338	likely_benign	0.1502	benign	-0.934	Destabilizing	0.007	N	0.393	neutral	None	None	None	None	N
N/C	0.1901	likely_benign	0.1896	benign	-0.13	Destabilizing	0.001	N	0.415	neutral	None	None	None	None	N
N/D	0.1126	likely_benign	0.1233	benign	-0.734	Destabilizing	0.029	N	0.295	neutral	D	0.529307163	None	None	N
N/E	0.2515	likely_benign	0.2866	benign	-0.654	Destabilizing	0.038	N	0.271	neutral	None	None	None	None	N
N/F	0.3271	likely_benign	0.3625	ambiguous	-0.779	Destabilizing	0.356	N	0.463	neutral	None	None	None	None	N
N/G	0.1785	likely_benign	0.1949	benign	-1.251	Destabilizing	0.016	N	0.279	neutral	None	None	None	None	N
N/H	0.0702	likely_benign	0.0765	benign	-0.998	Destabilizing	0.295	N	0.396	neutral	N	0.504238147	None	None	N
N/I	0.1345	likely_benign	0.1553	benign	-0.135	Destabilizing	0.171	N	0.479	neutral	N	0.514916501	None	None	N
N/K	0.1586	likely_benign	0.1887	benign	-0.287	Destabilizing	0.012	N	0.273	neutral	N	0.478299553	None	None	N
N/L	0.1536	likely_benign	0.1735	benign	-0.135	Destabilizing	0.038	N	0.452	neutral	None	None	None	None	N
N/M	0.2313	likely_benign	0.2481	benign	0.392	Stabilizing	0.628	D	0.429	neutral	None	None	None	None	N
N/P	0.7132	likely_pathogenic	0.6893	pathogenic	-0.372	Destabilizing	None	N	0.334	neutral	None	None	None	None	N
N/Q	0.1815	likely_benign	0.2118	benign	-1.004	Destabilizing	0.072	N	0.34	neutral	None	None	None	None	N
N/R	0.1433	likely_benign	0.1744	benign	-0.235	Destabilizing	None	N	0.252	neutral	None	None	None	None	N
N/S	0.0576	likely_benign	0.061	benign	-0.938	Destabilizing	None	N	0.123	neutral	N	0.457252277	None	None	N
N/T	0.0813	likely_benign	0.0861	benign	-0.671	Destabilizing	0.001	N	0.121	neutral	N	0.503544714	None	None	N
N/V	0.1504	likely_benign	0.1669	benign	-0.372	Destabilizing	0.072	N	0.441	neutral	None	None	None	None	N
N/W	0.5588	ambiguous	0.6048	pathogenic	-0.514	Destabilizing	0.864	D	0.486	neutral	None	None	None	None	N
N/Y	0.116	likely_benign	0.1284	benign	-0.31	Destabilizing	0.295	N	0.439	neutral	N	0.498280537	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.