TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32897	98914;98915;98916	chr2:178539246;178539245;178539244	chr2:179403973;179403972;179403971
N2AB	31256	93991;93992;93993	chr2:178539246;178539245;178539244	chr2:179403973;179403972;179403971
N2A	30329	91210;91211;91212	chr2:178539246;178539245;178539244	chr2:179403973;179403972;179403971
N2B	23832	71719;71720;71721	chr2:178539246;178539245;178539244	chr2:179403973;179403972;179403971
Novex-1	23957	72094;72095;72096	chr2:178539246;178539245;178539244	chr2:179403973;179403972;179403971
Novex-2	24024	72295;72296;72297	chr2:178539246;178539245;178539244	chr2:179403973;179403972;179403971
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: Fn3-128
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.543
• 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/R	None	None	0.999	D	0.833	0.71	0.810075726734	gnomAD-4.0.0	1.59389E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86454E-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	0.7881	likely_pathogenic	0.7668	pathogenic	-1.554	Destabilizing	0.982	D	0.605	neutral	D	0.616573476	None	None	N
P/C	0.9802	likely_pathogenic	0.9789	pathogenic	-2.142	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
P/D	0.999	likely_pathogenic	0.9994	pathogenic	-3.509	Highly Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
P/E	0.9971	likely_pathogenic	0.998	pathogenic	-3.406	Highly Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
P/F	0.9993	likely_pathogenic	0.9995	pathogenic	-0.852	Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
P/G	0.9874	likely_pathogenic	0.9889	pathogenic	-1.883	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
P/H	0.997	likely_pathogenic	0.9979	pathogenic	-1.331	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
P/I	0.9886	likely_pathogenic	0.9896	pathogenic	-0.676	Destabilizing	0.992	D	0.749	deleterious	None	None	None	None	N
P/K	0.998	likely_pathogenic	0.9987	pathogenic	-1.588	Destabilizing	0.998	D	0.808	deleterious	None	None	None	None	N
P/L	0.9606	likely_pathogenic	0.963	pathogenic	-0.676	Destabilizing	0.289	N	0.37	neutral	D	0.616977085	None	None	N
P/M	0.9936	likely_pathogenic	0.9945	pathogenic	-1.086	Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
P/N	0.9985	likely_pathogenic	0.9989	pathogenic	-2.054	Highly Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
P/Q	0.9944	likely_pathogenic	0.9959	pathogenic	-2.098	Highly Destabilizing	0.999	D	0.816	deleterious	D	0.617178889	None	None	N
P/R	0.9929	likely_pathogenic	0.9951	pathogenic	-1.233	Destabilizing	0.999	D	0.833	deleterious	D	0.616977085	None	None	N
P/S	0.964	likely_pathogenic	0.9641	pathogenic	-2.31	Highly Destabilizing	0.999	D	0.787	deleterious	D	0.61677528	None	None	N
P/T	0.9648	likely_pathogenic	0.9673	pathogenic	-2.108	Highly Destabilizing	0.998	D	0.769	deleterious	D	0.616977085	None	None	N
P/V	0.9588	likely_pathogenic	0.9592	pathogenic	-0.945	Destabilizing	0.992	D	0.708	prob.delet.	None	None	None	None	N
P/W	0.9997	likely_pathogenic	0.9998	pathogenic	-1.273	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
P/Y	0.9994	likely_pathogenic	0.9996	pathogenic	-0.981	Destabilizing	1.0	D	0.852	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.