TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6861	20806;20807;20808	chr2:178725623;178725622;178725621	chr2:179590350;179590349;179590348
N2AB	6544	19855;19856;19857	chr2:178725623;178725622;178725621	chr2:179590350;179590349;179590348
N2A	5617	17074;17075;17076	chr2:178725623;178725622;178725621	chr2:179590350;179590349;179590348
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-53
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.579
• Predicted PPI site: I

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/H	rs2079209158	None	0.295	N	0.329	0.167	0.210429274316	gnomAD-4.0.0	1.6431E-06	None	None	None	None	I	None	5.91506E-05	0	None	0	0	None	0	0	0	0	0
N/K	rs760063480	None	0.012	N	0.227	0.123	0.158396225186	gnomAD-4.0.0	6.94043E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.08171E-07	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	0.1553	likely_benign	0.1257	benign	-0.22	Destabilizing	0.016	N	0.329	neutral	None	None	None	None	I
N/C	0.2621	likely_benign	0.2059	benign	0.29	Stabilizing	0.676	D	0.371	neutral	None	None	None	None	I
N/D	0.1074	likely_benign	0.1016	benign	0.322	Stabilizing	None	N	0.07	neutral	N	0.363072679	None	None	I
N/E	0.2252	likely_benign	0.2046	benign	0.281	Stabilizing	0.001	N	0.081	neutral	None	None	None	None	I
N/F	0.4092	ambiguous	0.3368	benign	-0.682	Destabilizing	0.356	N	0.412	neutral	None	None	None	None	I
N/G	0.1855	likely_benign	0.1561	benign	-0.366	Destabilizing	0.016	N	0.225	neutral	None	None	None	None	I
N/H	0.0775	likely_benign	0.0717	benign	-0.392	Destabilizing	0.295	N	0.329	neutral	N	0.393395586	None	None	I
N/I	0.1718	likely_benign	0.1423	benign	0.07	Stabilizing	0.029	N	0.449	neutral	N	0.38279459	None	None	I
N/K	0.1479	likely_benign	0.139	benign	0.245	Stabilizing	0.012	N	0.227	neutral	N	0.362376459	None	None	I
N/L	0.1865	likely_benign	0.1562	benign	0.07	Stabilizing	0.016	N	0.419	neutral	None	None	None	None	I
N/M	0.2925	likely_benign	0.2502	benign	0.285	Stabilizing	0.356	N	0.383	neutral	None	None	None	None	I
N/P	0.305	likely_benign	0.2371	benign	-0.001	Destabilizing	0.072	N	0.418	neutral	None	None	None	None	I
N/Q	0.1803	likely_benign	0.1573	benign	-0.226	Destabilizing	0.072	N	0.267	neutral	None	None	None	None	I
N/R	0.1663	likely_benign	0.1583	benign	0.261	Stabilizing	0.072	N	0.27	neutral	None	None	None	None	I
N/S	0.0682	likely_benign	0.0628	benign	-0.03	Destabilizing	None	N	0.087	neutral	N	0.262196396	None	None	I
N/T	0.0974	likely_benign	0.0842	benign	0.073	Stabilizing	None	N	0.081	neutral	N	0.370884086	None	None	I
N/V	0.1838	likely_benign	0.1502	benign	-0.001	Destabilizing	0.001	N	0.229	neutral	None	None	None	None	I
N/W	0.6268	likely_pathogenic	0.5847	pathogenic	-0.705	Destabilizing	0.864	D	0.393	neutral	None	None	None	None	I
N/Y	0.1299	likely_benign	0.1165	benign	-0.403	Destabilizing	0.295	N	0.401	neutral	N	0.412597422	None	None	I

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.