TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26488	79687;79688;79689	chr2:178566670;178566669;178566668	chr2:179431397;179431396;179431395
N2AB	24847	74764;74765;74766	chr2:178566670;178566669;178566668	chr2:179431397;179431396;179431395
N2A	23920	71983;71984;71985	chr2:178566670;178566669;178566668	chr2:179431397;179431396;179431395
N2B	17423	52492;52493;52494	chr2:178566670;178566669;178566668	chr2:179431397;179431396;179431395
Novex-1	17548	52867;52868;52869	chr2:178566670;178566669;178566668	chr2:179431397;179431396;179431395
Novex-2	17615	53068;53069;53070	chr2:178566670;178566669;178566668	chr2:179431397;179431396;179431395
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-81
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.1025
• 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
P/L	None	None	1.0	D	0.837	0.706	0.908644682553	gnomAD-4.0.0	1.36894E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79906E-06	0	0
P/S	None	None	1.0	D	0.776	0.737	0.677927297446	gnomAD-4.0.0	1.59263E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85886E-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
P/A	0.8229	likely_pathogenic	0.685	pathogenic	-1.88	Destabilizing	0.999	D	0.824	deleterious	D	0.602509693	None	None	N
P/C	0.9911	likely_pathogenic	0.9855	pathogenic	-2.008	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
P/D	0.9993	likely_pathogenic	0.9991	pathogenic	-3.245	Highly Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
P/E	0.998	likely_pathogenic	0.9968	pathogenic	-3.14	Highly Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
P/F	0.9997	likely_pathogenic	0.9993	pathogenic	-1.184	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
P/G	0.9911	likely_pathogenic	0.9863	pathogenic	-2.255	Highly Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
P/H	0.9983	likely_pathogenic	0.9972	pathogenic	-1.726	Destabilizing	1.0	D	0.803	deleterious	D	0.648155048	None	None	N
P/I	0.9918	likely_pathogenic	0.9857	pathogenic	-0.873	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
P/K	0.999	likely_pathogenic	0.9984	pathogenic	-1.633	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
P/L	0.9719	likely_pathogenic	0.9503	pathogenic	-0.873	Destabilizing	1.0	D	0.837	deleterious	D	0.646944222	None	None	N
P/M	0.9955	likely_pathogenic	0.9925	pathogenic	-1.087	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
P/N	0.999	likely_pathogenic	0.9985	pathogenic	-1.931	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
P/Q	0.9969	likely_pathogenic	0.9949	pathogenic	-1.995	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
P/R	0.9964	likely_pathogenic	0.9946	pathogenic	-1.234	Destabilizing	1.0	D	0.853	deleterious	D	0.647953244	None	None	N
P/S	0.9852	likely_pathogenic	0.9707	pathogenic	-2.345	Highly Destabilizing	1.0	D	0.776	deleterious	D	0.622011523	None	None	N
P/T	0.9794	likely_pathogenic	0.9611	pathogenic	-2.133	Highly Destabilizing	1.0	D	0.785	deleterious	D	0.647953244	None	None	N
P/V	0.972	likely_pathogenic	0.9552	pathogenic	-1.183	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
P/W	0.9998	likely_pathogenic	0.9997	pathogenic	-1.574	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
P/Y	0.9995	likely_pathogenic	0.9991	pathogenic	-1.284	Destabilizing	1.0	D	0.847	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.