TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15939	48040;48041;48042	chr2:178617180;178617179;178617178	chr2:179481907;179481906;179481905
N2AB	14298	43117;43118;43119	chr2:178617180;178617179;178617178	chr2:179481907;179481906;179481905
N2A	13371	40336;40337;40338	chr2:178617180;178617179;178617178	chr2:179481907;179481906;179481905
N2B	6874	20845;20846;20847	chr2:178617180;178617179;178617178	chr2:179481907;179481906;179481905
Novex-1	6999	21220;21221;21222	chr2:178617180;178617179;178617178	chr2:179481907;179481906;179481905
Novex-2	7066	21421;21422;21423	chr2:178617180;178617179;178617178	chr2:179481907;179481906;179481905
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-3
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.5082
• 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
K/E	rs1408557748	0.354	None	N	0.124	0.128	0.156986980423	gnomAD-2.1.1	4.49E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.02E-05	0
K/I	rs760239452	None	0.055	N	0.557	0.133	0.362160248664	gnomAD-4.0.0	1.38222E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.81126E-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
K/A	0.126	likely_benign	0.1381	benign	0.042	Stabilizing	None	N	0.126	neutral	None	None	None	None	I
K/C	0.5557	ambiguous	0.5711	pathogenic	-0.226	Destabilizing	0.356	N	0.41	neutral	None	None	None	None	I
K/D	0.4167	ambiguous	0.4423	ambiguous	0.025	Stabilizing	0.016	N	0.367	neutral	None	None	None	None	I
K/E	0.1255	likely_benign	0.1318	benign	0.031	Stabilizing	None	N	0.124	neutral	N	0.434983636	None	None	I
K/F	0.6314	likely_pathogenic	0.6706	pathogenic	-0.198	Destabilizing	0.356	N	0.471	neutral	None	None	None	None	I
K/G	0.3142	likely_benign	0.3343	benign	-0.147	Destabilizing	0.007	N	0.345	neutral	None	None	None	None	I
K/H	0.2879	likely_benign	0.2947	benign	-0.406	Destabilizing	0.356	N	0.393	neutral	None	None	None	None	I
K/I	0.1976	likely_benign	0.2154	benign	0.457	Stabilizing	0.055	N	0.557	neutral	N	0.457722486	None	None	I
K/L	0.2164	likely_benign	0.2245	benign	0.457	Stabilizing	0.016	N	0.401	neutral	None	None	None	None	I
K/M	0.1583	likely_benign	0.1753	benign	0.195	Stabilizing	0.356	N	0.392	neutral	None	None	None	None	I
K/N	0.3141	likely_benign	0.3326	benign	0.198	Stabilizing	0.024	N	0.305	neutral	N	0.456601273	None	None	I
K/P	0.5579	ambiguous	0.6362	pathogenic	0.346	Stabilizing	0.072	N	0.422	neutral	None	None	None	None	I
K/Q	0.1129	likely_benign	0.1152	benign	0.047	Stabilizing	0.012	N	0.331	neutral	N	0.46284734	None	None	I
K/R	0.0864	likely_benign	0.0877	benign	-0.036	Destabilizing	0.012	N	0.357	neutral	N	0.461063984	None	None	I
K/S	0.2357	likely_benign	0.258	benign	-0.254	Destabilizing	0.007	N	0.263	neutral	None	None	None	None	I
K/T	0.1268	likely_benign	0.1484	benign	-0.102	Destabilizing	0.012	N	0.369	neutral	N	0.472698495	None	None	I
K/V	0.1765	likely_benign	0.1906	benign	0.346	Stabilizing	0.016	N	0.401	neutral	None	None	None	None	I
K/W	0.7465	likely_pathogenic	0.7579	pathogenic	-0.244	Destabilizing	0.864	D	0.396	neutral	None	None	None	None	I
K/Y	0.4831	ambiguous	0.4907	ambiguous	0.119	Stabilizing	0.356	N	0.462	neutral	None	None	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.