TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22002	66229;66230;66231	chr2:178582452;178582451;178582450	chr2:179447179;179447178;179447177
N2AB	20361	61306;61307;61308	chr2:178582452;178582451;178582450	chr2:179447179;179447178;179447177
N2A	19434	58525;58526;58527	chr2:178582452;178582451;178582450	chr2:179447179;179447178;179447177
N2B	12937	39034;39035;39036	chr2:178582452;178582451;178582450	chr2:179447179;179447178;179447177
Novex-1	13062	39409;39410;39411	chr2:178582452;178582451;178582450	chr2:179447179;179447178;179447177
Novex-2	13129	39610;39611;39612	chr2:178582452;178582451;178582450	chr2:179447179;179447178;179447177
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: Fn3-47
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.5099
• 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/K	rs756154183	0.12	0.904	N	0.279	0.164	0.193865811164	gnomAD-2.1.1	2.02E-05	None	None	None	None	N	None	0	1.45307E-04	None	0	0	None	0	None	0	0	0
N/K	rs756154183	0.12	0.904	N	0.279	0.164	0.193865811164	gnomAD-4.0.0	7.96541E-06	None	None	None	None	N	None	0	1.14432E-04	None	0	0	None	0	0	0	0	0
N/S	rs2047996309	None	0.698	N	0.373	0.2	0.141422826196	gnomAD-4.0.0	3.42275E-06	None	None	None	None	N	None	2.99204E-05	0	None	0	0	None	0	0	3.59901E-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
N/A	0.3792	ambiguous	0.3792	ambiguous	-0.154	Destabilizing	0.754	D	0.369	neutral	None	None	None	None	N
N/C	0.4648	ambiguous	0.455	ambiguous	0.14	Stabilizing	0.998	D	0.578	neutral	None	None	None	None	N
N/D	0.6219	likely_pathogenic	0.6316	pathogenic	0.191	Stabilizing	0.904	D	0.361	neutral	N	0.443789042	None	None	N
N/E	0.8677	likely_pathogenic	0.8646	pathogenic	0.158	Stabilizing	0.926	D	0.283	neutral	None	None	None	None	N
N/F	0.7341	likely_pathogenic	0.708	pathogenic	-0.678	Destabilizing	0.956	D	0.527	neutral	None	None	None	None	N
N/G	0.5024	ambiguous	0.4915	ambiguous	-0.281	Destabilizing	0.926	D	0.31	neutral	None	None	None	None	N
N/H	0.2784	likely_benign	0.2684	benign	-0.258	Destabilizing	0.99	D	0.329	neutral	N	0.490409553	None	None	N
N/I	0.3438	ambiguous	0.3378	benign	0.09	Stabilizing	0.89	D	0.471	neutral	N	0.47432538	None	None	N
N/K	0.8705	likely_pathogenic	0.858	pathogenic	0.065	Stabilizing	0.904	D	0.279	neutral	N	0.449330935	None	None	N
N/L	0.3383	likely_benign	0.3398	benign	0.09	Stabilizing	0.754	D	0.419	neutral	None	None	None	None	N
N/M	0.517	ambiguous	0.4997	ambiguous	-0.023	Destabilizing	0.994	D	0.474	neutral	None	None	None	None	N
N/P	0.8591	likely_pathogenic	0.8114	pathogenic	0.033	Stabilizing	0.993	D	0.463	neutral	None	None	None	None	N
N/Q	0.7116	likely_pathogenic	0.6926	pathogenic	-0.163	Destabilizing	0.993	D	0.292	neutral	None	None	None	None	N
N/R	0.8327	likely_pathogenic	0.8156	pathogenic	0.125	Stabilizing	0.978	D	0.311	neutral	None	None	None	None	N
N/S	0.1165	likely_benign	0.123	benign	-0.032	Destabilizing	0.698	D	0.373	neutral	N	0.441114096	None	None	N
N/T	0.2226	likely_benign	0.2327	benign	0.055	Stabilizing	0.058	N	0.194	neutral	N	0.401270416	None	None	N
N/V	0.2804	likely_benign	0.2795	benign	0.033	Stabilizing	0.043	N	0.345	neutral	None	None	None	None	N
N/W	0.9329	likely_pathogenic	0.9238	pathogenic	-0.81	Destabilizing	0.998	D	0.648	neutral	None	None	None	None	N
N/Y	0.3737	ambiguous	0.3557	ambiguous	-0.488	Destabilizing	0.97	D	0.466	neutral	N	0.47756053	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.