TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26287	79084;79085;79086	chr2:178567273;178567272;178567271	chr2:179432000;179431999;179431998
N2AB	24646	74161;74162;74163	chr2:178567273;178567272;178567271	chr2:179432000;179431999;179431998
N2A	23719	71380;71381;71382	chr2:178567273;178567272;178567271	chr2:179432000;179431999;179431998
N2B	17222	51889;51890;51891	chr2:178567273;178567272;178567271	chr2:179432000;179431999;179431998
Novex-1	17347	52264;52265;52266	chr2:178567273;178567272;178567271	chr2:179432000;179431999;179431998
Novex-2	17414	52465;52466;52467	chr2:178567273;178567272;178567271	chr2:179432000;179431999;179431998
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-79
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.1104
• 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/S	rs1451385344	None	1.0	D	0.767	0.791	0.811423192096	gnomAD-4.0.0	1.3744E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.01585E-07	1.1773E-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
P/A	0.9575	likely_pathogenic	0.9455	pathogenic	-1.603	Destabilizing	0.999	D	0.827	deleterious	D	0.648147869	None	None	N
P/C	0.996	likely_pathogenic	0.9948	pathogenic	-1.996	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
P/D	0.9998	likely_pathogenic	0.9997	pathogenic	-3.388	Highly Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
P/E	0.9994	likely_pathogenic	0.9993	pathogenic	-3.287	Highly Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
P/F	0.9999	likely_pathogenic	0.9998	pathogenic	-0.868	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
P/G	0.9973	likely_pathogenic	0.9968	pathogenic	-1.947	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
P/H	0.9994	likely_pathogenic	0.9992	pathogenic	-1.384	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
P/I	0.9969	likely_pathogenic	0.9964	pathogenic	-0.687	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
P/K	0.9995	likely_pathogenic	0.9995	pathogenic	-1.502	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
P/L	0.9878	likely_pathogenic	0.9861	pathogenic	-0.687	Destabilizing	1.0	D	0.83	deleterious	D	0.6536591	None	None	N
P/M	0.9986	likely_pathogenic	0.9984	pathogenic	-1.047	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
P/N	0.9997	likely_pathogenic	0.9997	pathogenic	-1.908	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
P/Q	0.9992	likely_pathogenic	0.9991	pathogenic	-1.959	Destabilizing	1.0	D	0.819	deleterious	D	0.686131791	None	None	N
P/R	0.9984	likely_pathogenic	0.998	pathogenic	-1.144	Destabilizing	1.0	D	0.844	deleterious	D	0.669910625	None	None	N
P/S	0.9968	likely_pathogenic	0.9959	pathogenic	-2.202	Highly Destabilizing	1.0	D	0.767	deleterious	D	0.685728182	None	None	N
P/T	0.9953	likely_pathogenic	0.9945	pathogenic	-2.001	Highly Destabilizing	1.0	D	0.774	deleterious	D	0.669910625	None	None	N
P/V	0.9905	likely_pathogenic	0.9883	pathogenic	-0.968	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
P/W	0.9999	likely_pathogenic	0.9999	pathogenic	-1.281	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
P/Y	0.9998	likely_pathogenic	0.9998	pathogenic	-0.991	Destabilizing	1.0	D	0.836	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.