TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23284	70075;70076;70077	chr2:178576282;178576281;178576280	chr2:179441009;179441008;179441007
N2AB	21643	65152;65153;65154	chr2:178576282;178576281;178576280	chr2:179441009;179441008;179441007
N2A	20716	62371;62372;62373	chr2:178576282;178576281;178576280	chr2:179441009;179441008;179441007
N2B	14219	42880;42881;42882	chr2:178576282;178576281;178576280	chr2:179441009;179441008;179441007
Novex-1	14344	43255;43256;43257	chr2:178576282;178576281;178576280	chr2:179441009;179441008;179441007
Novex-2	14411	43456;43457;43458	chr2:178576282;178576281;178576280	chr2:179441009;179441008;179441007
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-57
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.4655
• 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
D/V	rs768131129	0.283	0.317	N	0.431	0.33	0.408853032482	gnomAD-2.1.1	4.22E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.31E-06	0
D/V	rs768131129	0.283	0.317	N	0.431	0.33	0.408853032482	gnomAD-4.0.0	4.85197E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.67624E-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
D/A	0.1004	likely_benign	0.0986	benign	-0.108	Destabilizing	0.062	N	0.31	neutral	N	0.444501118	None	None	N
D/C	0.3632	ambiguous	0.3531	ambiguous	0.152	Stabilizing	0.935	D	0.507	neutral	None	None	None	None	N
D/E	0.0762	likely_benign	0.077	benign	-0.238	Destabilizing	None	N	0.185	neutral	N	0.412503343	None	None	N
D/F	0.4358	ambiguous	0.4308	ambiguous	-0.221	Destabilizing	0.555	D	0.453	neutral	None	None	None	None	N
D/G	0.1087	likely_benign	0.1047	benign	-0.267	Destabilizing	0.117	N	0.259	neutral	N	0.416274367	None	None	N
D/H	0.1746	likely_benign	0.1689	benign	-0.018	Destabilizing	None	N	0.289	neutral	N	0.505722935	None	None	N
D/I	0.2389	likely_benign	0.2346	benign	0.25	Stabilizing	0.555	D	0.452	neutral	None	None	None	None	N
D/K	0.1648	likely_benign	0.1667	benign	0.433	Stabilizing	0.081	N	0.259	neutral	None	None	None	None	N
D/L	0.2137	likely_benign	0.2107	benign	0.25	Stabilizing	0.38	N	0.427	neutral	None	None	None	None	N
D/M	0.336	likely_benign	0.3326	benign	0.328	Stabilizing	0.935	D	0.464	neutral	None	None	None	None	N
D/N	0.0776	likely_benign	0.0762	benign	0.279	Stabilizing	0.117	N	0.297	neutral	N	0.457736987	None	None	N
D/P	0.6891	likely_pathogenic	0.6689	pathogenic	0.152	Stabilizing	0.555	D	0.328	neutral	None	None	None	None	N
D/Q	0.1503	likely_benign	0.1488	benign	0.277	Stabilizing	0.081	N	0.279	neutral	None	None	None	None	N
D/R	0.2213	likely_benign	0.2174	benign	0.538	Stabilizing	0.235	N	0.385	neutral	None	None	None	None	N
D/S	0.0758	likely_benign	0.075	benign	0.16	Stabilizing	0.081	N	0.253	neutral	None	None	None	None	N
D/T	0.1171	likely_benign	0.1145	benign	0.277	Stabilizing	0.149	N	0.298	neutral	None	None	None	None	N
D/V	0.1303	likely_benign	0.1295	benign	0.152	Stabilizing	0.317	N	0.431	neutral	N	0.471495718	None	None	N
D/W	0.7671	likely_pathogenic	0.7617	pathogenic	-0.163	Destabilizing	0.935	D	0.553	neutral	None	None	None	None	N
D/Y	0.1869	likely_benign	0.185	benign	0.004	Stabilizing	0.317	N	0.453	neutral	N	0.471747178	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.