TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7624	23095;23096;23097	chr2:178721149;178721148;178721147	chr2:179585876;179585875;179585874
N2AB	7307	22144;22145;22146	chr2:178721149;178721148;178721147	chr2:179585876;179585875;179585874
N2A	6380	19363;19364;19365	chr2:178721149;178721148;178721147	chr2:179585876;179585875;179585874
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-61
• Domain position: 17
• Structural Position: 25
• Q(SASA): 0.3977
• 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
E/K	rs2078297140	None	0.518	N	0.24	0.11	0.167679373172	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs2078297140	None	0.518	N	0.24	0.11	0.167679373172	gnomAD-4.0.0	2.57533E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.821E-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
E/A	0.175	likely_benign	0.1732	benign	-0.534	Destabilizing	0.107	N	0.301	neutral	N	0.509872387	None	None	N
E/C	0.8554	likely_pathogenic	0.8583	pathogenic	0.068	Stabilizing	0.984	D	0.376	neutral	None	None	None	None	N
E/D	0.0755	likely_benign	0.07	benign	-0.383	Destabilizing	None	N	0.131	neutral	N	0.419634385	None	None	N
E/F	0.7314	likely_pathogenic	0.7416	pathogenic	-0.412	Destabilizing	0.91	D	0.365	neutral	None	None	None	None	N
E/G	0.1764	likely_benign	0.178	benign	-0.749	Destabilizing	0.003	N	0.165	neutral	N	0.498057883	None	None	N
E/H	0.439	ambiguous	0.4556	ambiguous	-0.349	Destabilizing	0.957	D	0.297	neutral	None	None	None	None	N
E/I	0.4224	ambiguous	0.4464	ambiguous	0.006	Stabilizing	0.7	D	0.383	neutral	None	None	None	None	N
E/K	0.1735	likely_benign	0.1914	benign	0.404	Stabilizing	0.518	D	0.24	neutral	N	0.473719586	None	None	N
E/L	0.4445	ambiguous	0.4595	ambiguous	0.006	Stabilizing	0.25	N	0.368	neutral	None	None	None	None	N
E/M	0.4738	ambiguous	0.4774	ambiguous	0.267	Stabilizing	0.907	D	0.345	neutral	None	None	None	None	N
E/N	0.1875	likely_benign	0.1833	benign	0.019	Stabilizing	0.134	N	0.21	neutral	None	None	None	None	N
E/P	0.879	likely_pathogenic	0.8948	pathogenic	-0.154	Destabilizing	0.413	N	0.311	neutral	None	None	None	None	N
E/Q	0.1365	likely_benign	0.1442	benign	0.06	Stabilizing	0.609	D	0.315	neutral	N	0.444916832	None	None	N
E/R	0.3143	likely_benign	0.3361	benign	0.506	Stabilizing	0.91	D	0.279	neutral	None	None	None	None	N
E/S	0.1731	likely_benign	0.1697	benign	-0.134	Destabilizing	0.137	N	0.24	neutral	None	None	None	None	N
E/T	0.2371	likely_benign	0.2422	benign	0.05	Stabilizing	0.014	N	0.204	neutral	None	None	None	None	N
E/V	0.2476	likely_benign	0.262	benign	-0.154	Destabilizing	0.152	N	0.369	neutral	N	0.474182125	None	None	N
E/W	0.902	likely_pathogenic	0.9112	pathogenic	-0.226	Destabilizing	0.997	D	0.422	neutral	None	None	None	None	N
E/Y	0.592	likely_pathogenic	0.6067	pathogenic	-0.15	Destabilizing	0.988	D	0.348	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.