TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6896	20911;20912;20913	chr2:178725518;178725517;178725516	chr2:179590245;179590244;179590243
N2AB	6579	19960;19961;19962	chr2:178725518;178725517;178725516	chr2:179590245;179590244;179590243
N2A	5652	17179;17180;17181	chr2:178725518;178725517;178725516	chr2:179590245;179590244;179590243
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: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-53
• Domain position: 43
• Structural Position: 59
• Q(SASA): 0.7772
• 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
R/K	rs1026814261	None	0.4	N	0.267	0.19	0.282575091529	gnomAD-4.0.0	3.42217E-06	None	None	None	None	N	None	2.99115E-05	0	None	0	0	None	0	0	1.79936E-06	0	3.31433E-05
R/S	None	None	0.98	N	0.577	0.332	0.490839437361	gnomAD-4.0.0	1.59236E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86026E-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
R/A	0.4601	ambiguous	0.5097	ambiguous	0.064	Stabilizing	0.964	D	0.589	neutral	None	None	None	None	N
R/C	0.3398	likely_benign	0.3741	ambiguous	-0.324	Destabilizing	1.0	D	0.619	neutral	None	None	None	None	N
R/D	0.7289	likely_pathogenic	0.7722	pathogenic	-0.351	Destabilizing	0.998	D	0.502	neutral	None	None	None	None	N
R/E	0.3443	ambiguous	0.4054	ambiguous	-0.305	Destabilizing	0.985	D	0.551	neutral	None	None	None	None	N
R/F	0.6127	likely_pathogenic	0.6722	pathogenic	-0.269	Destabilizing	0.999	D	0.591	neutral	None	None	None	None	N
R/G	0.289	likely_benign	0.333	benign	-0.074	Destabilizing	0.135	N	0.345	neutral	N	0.491759624	None	None	N
R/H	0.1589	likely_benign	0.1582	benign	-0.596	Destabilizing	0.999	D	0.533	neutral	None	None	None	None	N
R/I	0.3918	ambiguous	0.44	ambiguous	0.381	Stabilizing	0.999	D	0.594	neutral	N	0.503534003	None	None	N
R/K	0.15	likely_benign	0.1397	benign	-0.209	Destabilizing	0.4	N	0.267	neutral	N	0.510430614	None	None	N
R/L	0.3299	likely_benign	0.3779	ambiguous	0.381	Stabilizing	0.993	D	0.523	neutral	None	None	None	None	N
R/M	0.3849	ambiguous	0.4313	ambiguous	-0.127	Destabilizing	1.0	D	0.551	neutral	None	None	None	None	N
R/N	0.6941	likely_pathogenic	0.7156	pathogenic	-0.212	Destabilizing	0.993	D	0.543	neutral	None	None	None	None	N
R/P	0.5937	likely_pathogenic	0.6631	pathogenic	0.294	Stabilizing	0.999	D	0.575	neutral	None	None	None	None	N
R/Q	0.1226	likely_benign	0.1302	benign	-0.204	Destabilizing	0.996	D	0.553	neutral	None	None	None	None	N
R/S	0.5515	ambiguous	0.6003	pathogenic	-0.338	Destabilizing	0.98	D	0.577	neutral	N	0.520282248	None	None	N
R/T	0.2791	likely_benign	0.3144	benign	-0.186	Destabilizing	0.99	D	0.553	neutral	N	0.493866438	None	None	N
R/V	0.4567	ambiguous	0.4929	ambiguous	0.294	Stabilizing	0.998	D	0.564	neutral	None	None	None	None	N
R/W	0.168	likely_benign	0.2183	benign	-0.485	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	N
R/Y	0.4817	ambiguous	0.5508	ambiguous	-0.072	Destabilizing	0.999	D	0.571	neutral	None	None	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.