TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22093	66502;66503;66504	chr2:178582092;178582091;178582090	chr2:179446819;179446818;179446817
N2AB	20452	61579;61580;61581	chr2:178582092;178582091;178582090	chr2:179446819;179446818;179446817
N2A	19525	58798;58799;58800	chr2:178582092;178582091;178582090	chr2:179446819;179446818;179446817
N2B	13028	39307;39308;39309	chr2:178582092;178582091;178582090	chr2:179446819;179446818;179446817
Novex-1	13153	39682;39683;39684	chr2:178582092;178582091;178582090	chr2:179446819;179446818;179446817
Novex-2	13220	39883;39884;39885	chr2:178582092;178582091;178582090	chr2:179446819;179446818;179446817
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-48
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1809
• 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
E/D	None	None	0.999	N	0.631	0.224	0.367612772649	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/V	None	None	1.0	D	0.755	0.55	0.586996327016	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
E/A	0.9407	likely_pathogenic	0.9206	pathogenic	-1.66	Destabilizing	0.999	D	0.682	prob.neutral	D	0.527126808	None	None	N
E/C	0.9907	likely_pathogenic	0.9884	pathogenic	-0.846	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
E/D	0.6643	likely_pathogenic	0.6427	pathogenic	-1.748	Destabilizing	0.999	D	0.631	neutral	N	0.481132155	None	None	N
E/F	0.991	likely_pathogenic	0.9905	pathogenic	-1.288	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
E/G	0.9399	likely_pathogenic	0.9199	pathogenic	-2.065	Highly Destabilizing	1.0	D	0.75	deleterious	D	0.535649184	None	None	N
E/H	0.9639	likely_pathogenic	0.9589	pathogenic	-1.178	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
E/I	0.9812	likely_pathogenic	0.9805	pathogenic	-0.493	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
E/K	0.9538	likely_pathogenic	0.9494	pathogenic	-1.548	Destabilizing	0.999	D	0.673	neutral	N	0.509730115	None	None	N
E/L	0.9699	likely_pathogenic	0.9679	pathogenic	-0.493	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
E/M	0.9763	likely_pathogenic	0.9735	pathogenic	0.26	Stabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
E/N	0.9681	likely_pathogenic	0.9654	pathogenic	-1.794	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/P	0.9997	likely_pathogenic	0.9997	pathogenic	-0.868	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
E/Q	0.6238	likely_pathogenic	0.6188	pathogenic	-1.514	Destabilizing	1.0	D	0.73	prob.delet.	N	0.47038128	None	None	N
E/R	0.9563	likely_pathogenic	0.9515	pathogenic	-1.341	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/S	0.9308	likely_pathogenic	0.9161	pathogenic	-2.461	Highly Destabilizing	0.999	D	0.726	prob.delet.	None	None	None	None	N
E/T	0.972	likely_pathogenic	0.9664	pathogenic	-2.075	Highly Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
E/V	0.952	likely_pathogenic	0.9457	pathogenic	-0.868	Destabilizing	1.0	D	0.755	deleterious	D	0.527887277	None	None	N
E/W	0.9916	likely_pathogenic	0.9912	pathogenic	-1.301	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/Y	0.9832	likely_pathogenic	0.9819	pathogenic	-1.074	Destabilizing	1.0	D	0.799	deleterious	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.