TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20080	60463;60464;60465	chr2:178591487;178591486;178591485	chr2:179456214;179456213;179456212
N2AB	18439	55540;55541;55542	chr2:178591487;178591486;178591485	chr2:179456214;179456213;179456212
N2A	17512	52759;52760;52761	chr2:178591487;178591486;178591485	chr2:179456214;179456213;179456212
N2B	11015	33268;33269;33270	chr2:178591487;178591486;178591485	chr2:179456214;179456213;179456212
Novex-1	11140	33643;33644;33645	chr2:178591487;178591486;178591485	chr2:179456214;179456213;179456212
Novex-2	11207	33844;33845;33846	chr2:178591487;178591486;178591485	chr2:179456214;179456213;179456212
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-120
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.0903
• 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
L/V	rs1559592788	None	0.003	N	0.211	0.111	0.209622950755	gnomAD-2.1.1	4.44E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.42E-06	0
L/V	rs1559592788	None	0.003	N	0.211	0.111	0.209622950755	gnomAD-4.0.0	2.78783E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.71797E-06	1.23907E-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
L/A	0.835	likely_pathogenic	0.8407	pathogenic	-1.699	Destabilizing	0.415	N	0.431	neutral	None	None	None	None	N
L/C	0.9094	likely_pathogenic	0.9184	pathogenic	-1.133	Destabilizing	0.996	D	0.54	neutral	None	None	None	None	N
L/D	0.9939	likely_pathogenic	0.9918	pathogenic	-1.298	Destabilizing	0.987	D	0.553	neutral	None	None	None	None	N
L/E	0.9696	likely_pathogenic	0.9662	pathogenic	-1.217	Destabilizing	0.961	D	0.535	neutral	None	None	None	None	N
L/F	0.565	likely_pathogenic	0.5521	ambiguous	-0.992	Destabilizing	0.923	D	0.537	neutral	None	None	None	None	N
L/G	0.9687	likely_pathogenic	0.9636	pathogenic	-2.08	Highly Destabilizing	0.961	D	0.535	neutral	None	None	None	None	N
L/H	0.9594	likely_pathogenic	0.9524	pathogenic	-1.226	Destabilizing	0.996	D	0.577	neutral	None	None	None	None	N
L/I	0.1424	likely_benign	0.176	benign	-0.685	Destabilizing	0.008	N	0.203	neutral	N	0.444778838	None	None	N
L/K	0.9489	likely_pathogenic	0.9365	pathogenic	-1.336	Destabilizing	0.961	D	0.502	neutral	None	None	None	None	N
L/M	0.1869	likely_benign	0.2021	benign	-0.669	Destabilizing	0.923	D	0.573	neutral	None	None	None	None	N
L/N	0.9673	likely_pathogenic	0.9619	pathogenic	-1.338	Destabilizing	0.987	D	0.568	neutral	None	None	None	None	N
L/P	0.9209	likely_pathogenic	0.9128	pathogenic	-0.995	Destabilizing	0.983	D	0.554	neutral	N	0.488905106	None	None	N
L/Q	0.9218	likely_pathogenic	0.9187	pathogenic	-1.37	Destabilizing	0.983	D	0.551	neutral	N	0.488651617	None	None	N
L/R	0.9347	likely_pathogenic	0.9198	pathogenic	-0.874	Destabilizing	0.983	D	0.532	neutral	N	0.487384169	None	None	N
L/S	0.9645	likely_pathogenic	0.9611	pathogenic	-1.945	Destabilizing	0.961	D	0.476	neutral	None	None	None	None	N
L/T	0.7569	likely_pathogenic	0.7615	pathogenic	-1.73	Destabilizing	0.775	D	0.47	neutral	None	None	None	None	N
L/V	0.1658	likely_benign	0.2111	benign	-0.995	Destabilizing	0.003	N	0.211	neutral	N	0.4567667	None	None	N
L/W	0.8675	likely_pathogenic	0.8328	pathogenic	-1.131	Destabilizing	0.996	D	0.585	neutral	None	None	None	None	N
L/Y	0.9204	likely_pathogenic	0.9056	pathogenic	-0.894	Destabilizing	0.961	D	0.531	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.