TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30325	91198;91199;91200	chr2:178551927;178551926;178551925	chr2:179416654;179416653;179416652
N2AB	28684	86275;86276;86277	chr2:178551927;178551926;178551925	chr2:179416654;179416653;179416652
N2A	27757	83494;83495;83496	chr2:178551927;178551926;178551925	chr2:179416654;179416653;179416652
N2B	21260	64003;64004;64005	chr2:178551927;178551926;178551925	chr2:179416654;179416653;179416652
Novex-1	21385	64378;64379;64380	chr2:178551927;178551926;178551925	chr2:179416654;179416653;179416652
Novex-2	21452	64579;64580;64581	chr2:178551927;178551926;178551925	chr2:179416654;179416653;179416652
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: Fn3-109
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.1247
• 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/A	None	None	0.999	D	0.801	0.717	0.736517613924	gnomAD-4.0.0	3.42126E-06	None	None	None	None	N	None	0	0	None	0	7.5582E-05	None	0	0	0	0	3.31312E-05
P/S	None	None	1.0	D	0.739	0.736	0.746115941231	gnomAD-4.0.0	6.84252E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15953E-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	0.7541	likely_pathogenic	0.8449	pathogenic	-1.715	Destabilizing	0.999	D	0.801	deleterious	D	0.620055946	None	None	N
P/C	0.9783	likely_pathogenic	0.9859	pathogenic	-2.221	Highly Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
P/D	0.9993	likely_pathogenic	0.9994	pathogenic	-3.377	Highly Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
P/E	0.9971	likely_pathogenic	0.998	pathogenic	-3.278	Highly Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
P/F	0.9989	likely_pathogenic	0.9994	pathogenic	-1.124	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
P/G	0.9892	likely_pathogenic	0.9927	pathogenic	-2.055	Highly Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
P/H	0.9948	likely_pathogenic	0.9966	pathogenic	-1.482	Destabilizing	1.0	D	0.776	deleterious	D	0.658039868	None	None	N
P/I	0.9783	likely_pathogenic	0.9888	pathogenic	-0.816	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
P/K	0.9977	likely_pathogenic	0.9982	pathogenic	-1.614	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
P/L	0.9331	likely_pathogenic	0.9564	pathogenic	-0.816	Destabilizing	1.0	D	0.815	deleterious	D	0.657838063	None	None	N
P/M	0.9919	likely_pathogenic	0.9956	pathogenic	-1.209	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
P/N	0.9986	likely_pathogenic	0.999	pathogenic	-1.99	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
P/Q	0.992	likely_pathogenic	0.9952	pathogenic	-2.083	Highly Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
P/R	0.9888	likely_pathogenic	0.9916	pathogenic	-1.212	Destabilizing	1.0	D	0.817	deleterious	D	0.641586538	None	None	N
P/S	0.9674	likely_pathogenic	0.9811	pathogenic	-2.343	Highly Destabilizing	1.0	D	0.739	deleterious	D	0.641384734	None	None	N
P/T	0.9506	likely_pathogenic	0.9743	pathogenic	-2.139	Highly Destabilizing	1.0	D	0.747	deleterious	D	0.641586538	None	None	N
P/V	0.9449	likely_pathogenic	0.97	pathogenic	-1.091	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
P/W	0.9996	likely_pathogenic	0.9997	pathogenic	-1.475	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
P/Y	0.9991	likely_pathogenic	0.9995	pathogenic	-1.159	Destabilizing	1.0	D	0.848	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.