TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25602	77029;77030;77031	chr2:178569328;178569327;178569326	chr2:179434055;179434054;179434053
N2AB	23961	72106;72107;72108	chr2:178569328;178569327;178569326	chr2:179434055;179434054;179434053
N2A	23034	69325;69326;69327	chr2:178569328;178569327;178569326	chr2:179434055;179434054;179434053
N2B	16537	49834;49835;49836	chr2:178569328;178569327;178569326	chr2:179434055;179434054;179434053
Novex-1	16662	50209;50210;50211	chr2:178569328;178569327;178569326	chr2:179434055;179434054;179434053
Novex-2	16729	50410;50411;50412	chr2:178569328;178569327;178569326	chr2:179434055;179434054;179434053
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: Fn3-74
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.1085
• 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	rs1707254187	None	0.997	D	0.717	0.704	0.735842215327	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
P/S	rs1707254187	None	0.997	D	0.717	0.704	0.735842215327	gnomAD-4.0.0	2.03009E-06	None	None	None	None	N	None	1.7477E-05	0	None	0	0	None	0	0	1.20498E-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	0.888	likely_pathogenic	0.8909	pathogenic	-1.609	Destabilizing	0.94	D	0.685	prob.delet.	D	0.654648479	None	None	N
P/C	0.9945	likely_pathogenic	0.9948	pathogenic	-2.114	Highly Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
P/D	0.9997	likely_pathogenic	0.9997	pathogenic	-3.256	Highly Destabilizing	0.977	D	0.793	deleterious	None	None	None	None	N
P/E	0.9993	likely_pathogenic	0.9994	pathogenic	-3.186	Highly Destabilizing	0.957	D	0.769	deleterious	None	None	None	None	N
P/F	0.9998	likely_pathogenic	0.9998	pathogenic	-1.184	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
P/G	0.9963	likely_pathogenic	0.9965	pathogenic	-1.928	Destabilizing	0.997	D	0.793	deleterious	None	None	None	None	N
P/H	0.999	likely_pathogenic	0.9992	pathogenic	-1.338	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
P/I	0.9947	likely_pathogenic	0.9954	pathogenic	-0.786	Destabilizing	0.999	D	0.798	deleterious	None	None	None	None	N
P/K	0.9996	likely_pathogenic	0.9996	pathogenic	-1.532	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
P/L	0.9792	likely_pathogenic	0.984	pathogenic	-0.786	Destabilizing	0.856	D	0.677	prob.neutral	D	0.680590199	None	None	N
P/M	0.9979	likely_pathogenic	0.9982	pathogenic	-1.108	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
P/N	0.9995	likely_pathogenic	0.9995	pathogenic	-1.848	Destabilizing	0.996	D	0.824	deleterious	None	None	None	None	N
P/Q	0.9985	likely_pathogenic	0.9987	pathogenic	-2.009	Highly Destabilizing	0.998	D	0.806	deleterious	D	0.680792004	None	None	N
P/R	0.9979	likely_pathogenic	0.9983	pathogenic	-1.072	Destabilizing	0.998	D	0.825	deleterious	D	0.680590199	None	None	N
P/S	0.9866	likely_pathogenic	0.9875	pathogenic	-2.195	Highly Destabilizing	0.997	D	0.717	prob.delet.	D	0.664136869	None	None	N
P/T	0.987	likely_pathogenic	0.988	pathogenic	-2.023	Highly Destabilizing	0.988	D	0.747	deleterious	D	0.680590199	None	None	N
P/V	0.9798	likely_pathogenic	0.9818	pathogenic	-1.033	Destabilizing	0.997	D	0.801	deleterious	None	None	None	None	N
P/W	0.9999	likely_pathogenic	1.0	pathogenic	-1.488	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
P/Y	0.9998	likely_pathogenic	0.9999	pathogenic	-1.148	Destabilizing	1.0	D	0.828	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.