TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32976	99151;99152;99153	chr2:178539009;178539008;178539007	chr2:179403736;179403735;179403734
N2AB	31335	94228;94229;94230	chr2:178539009;178539008;178539007	chr2:179403736;179403735;179403734
N2A	30408	91447;91448;91449	chr2:178539009;178539008;178539007	chr2:179403736;179403735;179403734
N2B	23911	71956;71957;71958	chr2:178539009;178539008;178539007	chr2:179403736;179403735;179403734
Novex-1	24036	72331;72332;72333	chr2:178539009;178539008;178539007	chr2:179403736;179403735;179403734
Novex-2	24103	72532;72533;72534	chr2:178539009;178539008;178539007	chr2:179403736;179403735;179403734
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-128
• Domain position: 81
• Structural Position: 112
• Q(SASA): 0.0768
• 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	rs768961283	-0.035	1.0	D	0.761	0.587	0.229924730088	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
N/K	rs768961283	-0.035	1.0	D	0.761	0.587	0.229924730088	gnomAD-4.0.0	1.59152E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85892E-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	0.9988	likely_pathogenic	0.9982	pathogenic	0.097	Stabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
N/C	0.9911	likely_pathogenic	0.9867	pathogenic	-0.343	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
N/D	0.9926	likely_pathogenic	0.9875	pathogenic	-2.401	Highly Destabilizing	0.999	D	0.602	neutral	D	0.552644711	None	None	N
N/E	0.9993	likely_pathogenic	0.9992	pathogenic	-2.253	Highly Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
N/F	0.9998	likely_pathogenic	0.9997	pathogenic	-0.164	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
N/G	0.994	likely_pathogenic	0.9899	pathogenic	-0.153	Destabilizing	0.999	D	0.586	neutral	None	None	None	None	N
N/H	0.9942	likely_pathogenic	0.991	pathogenic	-0.12	Destabilizing	1.0	D	0.79	deleterious	D	0.554419138	None	None	N
N/I	0.9985	likely_pathogenic	0.9978	pathogenic	0.692	Stabilizing	1.0	D	0.834	deleterious	D	0.554672627	None	None	N
N/K	0.9991	likely_pathogenic	0.9988	pathogenic	0.179	Stabilizing	1.0	D	0.761	deleterious	D	0.55340518	None	None	N
N/L	0.995	likely_pathogenic	0.9933	pathogenic	0.692	Stabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
N/M	0.9976	likely_pathogenic	0.9966	pathogenic	0.698	Stabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
N/P	0.9993	likely_pathogenic	0.9991	pathogenic	0.522	Stabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
N/Q	0.9994	likely_pathogenic	0.9993	pathogenic	-0.831	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
N/R	0.9984	likely_pathogenic	0.9984	pathogenic	0.173	Stabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
N/S	0.9643	likely_pathogenic	0.9305	pathogenic	-0.555	Destabilizing	0.999	D	0.599	neutral	N	0.515422243	None	None	N
N/T	0.9828	likely_pathogenic	0.9777	pathogenic	-0.287	Destabilizing	0.999	D	0.724	prob.delet.	N	0.502518547	None	None	N
N/V	0.9978	likely_pathogenic	0.9968	pathogenic	0.522	Stabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
N/W	0.9999	likely_pathogenic	0.9998	pathogenic	-0.414	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
N/Y	0.9974	likely_pathogenic	0.996	pathogenic	0.206	Stabilizing	1.0	D	0.851	deleterious	D	0.554419138	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.