TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27643	83152;83153;83154	chr2:178563205;178563204;178563203	chr2:179427932;179427931;179427930
N2AB	26002	78229;78230;78231	chr2:178563205;178563204;178563203	chr2:179427932;179427931;179427930
N2A	25075	75448;75449;75450	chr2:178563205;178563204;178563203	chr2:179427932;179427931;179427930
N2B	18578	55957;55958;55959	chr2:178563205;178563204;178563203	chr2:179427932;179427931;179427930
Novex-1	18703	56332;56333;56334	chr2:178563205;178563204;178563203	chr2:179427932;179427931;179427930
Novex-2	18770	56533;56534;56535	chr2:178563205;178563204;178563203	chr2:179427932;179427931;179427930
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: Fn3-89
• Domain position: 74
• Structural Position: 105
• Q(SASA): 0.2326
• 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	rs1457183253	-1.802	0.379	N	0.634	0.134	0.177238962908	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
N/D	rs1457183253	-1.802	0.379	N	0.634	0.134	0.177238962908	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	4.14422E-04	0
N/D	rs1457183253	-1.802	0.379	N	0.634	0.134	0.177238962908	gnomAD-4.0.0	7.68596E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	8.04074E-05	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	0.1513	likely_benign	0.1752	benign	-1.734	Destabilizing	0.25	N	0.587	neutral	None	None	None	None	N
N/C	0.1071	likely_benign	0.133	benign	-0.68	Destabilizing	0.026	N	0.577	neutral	None	None	None	None	N
N/D	0.1566	likely_benign	0.1548	benign	-1.767	Destabilizing	0.379	N	0.634	neutral	N	0.503936211	None	None	N
N/E	0.3033	likely_benign	0.3227	benign	-1.469	Destabilizing	0.005	N	0.463	neutral	None	None	None	None	N
N/F	0.3324	likely_benign	0.3797	ambiguous	-1.109	Destabilizing	0.92	D	0.682	prob.neutral	None	None	None	None	N
N/G	0.2778	likely_benign	0.3065	benign	-2.157	Highly Destabilizing	0.25	N	0.594	neutral	None	None	None	None	N
N/H	0.0693	likely_benign	0.0759	benign	-1.242	Destabilizing	0.896	D	0.593	neutral	N	0.477000326	None	None	N
N/I	0.1117	likely_benign	0.1233	benign	-0.564	Destabilizing	0.81	D	0.67	neutral	N	0.465687254	None	None	N
N/K	0.2466	likely_benign	0.254	benign	-0.088	Destabilizing	0.016	N	0.467	neutral	N	0.403329286	None	None	N
N/L	0.1336	likely_benign	0.1461	benign	-0.564	Destabilizing	0.447	N	0.593	neutral	None	None	None	None	N
N/M	0.2062	likely_benign	0.2452	benign	-0.434	Destabilizing	0.992	D	0.637	neutral	None	None	None	None	N
N/P	0.908	likely_pathogenic	0.8888	pathogenic	-0.932	Destabilizing	0.92	D	0.618	neutral	None	None	None	None	N
N/Q	0.2031	likely_benign	0.2279	benign	-0.622	Destabilizing	0.739	D	0.58	neutral	None	None	None	None	N
N/R	0.2427	likely_benign	0.2458	benign	-0.234	Destabilizing	0.447	N	0.563	neutral	None	None	None	None	N
N/S	0.0668	likely_benign	0.0722	benign	-1.303	Destabilizing	0.007	N	0.295	neutral	N	0.440250092	None	None	N
N/T	0.089	likely_benign	0.1	benign	-0.805	Destabilizing	0.379	N	0.597	neutral	N	0.442442248	None	None	N
N/V	0.1179	likely_benign	0.1335	benign	-0.932	Destabilizing	0.617	D	0.645	neutral	None	None	None	None	N
N/W	0.6393	likely_pathogenic	0.655	pathogenic	-0.861	Destabilizing	0.992	D	0.724	prob.delet.	None	None	None	None	N
N/Y	0.1155	likely_benign	0.1231	benign	-0.58	Destabilizing	0.963	D	0.639	neutral	N	0.473133301	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.