TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10164	30715;30716;30717	chr2:178702189;178702188;178702187	chr2:179566916;179566915;179566914
N2AB	9847	29764;29765;29766	chr2:178702189;178702188;178702187	chr2:179566916;179566915;179566914
N2A	8920	26983;26984;26985	chr2:178702189;178702188;178702187	chr2:179566916;179566915;179566914
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-86
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.2747
• 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
E/D	rs1064797276	-0.862	0.999	None	0.486	0.131	0.267755039894	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/D	rs1064797276	-0.862	0.999	None	0.486	0.131	0.267755039894	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/D	rs1064797276	-0.862	0.999	None	0.486	0.131	0.267755039894	gnomAD-4.0.0	6.84134E-07	None	None	None	None	N	None	0	2.23594E-05	None	0	0	None	0	0	0	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
E/A	0.8255	likely_pathogenic	0.8493	pathogenic	-0.912	Destabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	N
E/C	0.995	likely_pathogenic	0.9959	pathogenic	-0.368	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/D	0.8835	likely_pathogenic	0.9194	pathogenic	-0.915	Destabilizing	0.999	D	0.486	neutral	None	None	None	None	N
E/F	0.9923	likely_pathogenic	0.9935	pathogenic	-0.053	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
E/G	0.9372	likely_pathogenic	0.9481	pathogenic	-1.315	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
E/H	0.9709	likely_pathogenic	0.9754	pathogenic	-0.169	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
E/I	0.9522	likely_pathogenic	0.9619	pathogenic	0.206	Stabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
E/K	0.8552	likely_pathogenic	0.879	pathogenic	-0.29	Destabilizing	0.999	D	0.623	neutral	None	None	None	None	N
E/L	0.9685	likely_pathogenic	0.9742	pathogenic	0.206	Stabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
E/M	0.9592	likely_pathogenic	0.9656	pathogenic	0.672	Stabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
E/N	0.9505	likely_pathogenic	0.9613	pathogenic	-1.001	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/P	0.9971	likely_pathogenic	0.9968	pathogenic	-0.146	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
E/Q	0.6662	likely_pathogenic	0.7084	pathogenic	-0.83	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
E/R	0.8997	likely_pathogenic	0.9114	pathogenic	0.027	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/S	0.8801	likely_pathogenic	0.8965	pathogenic	-1.354	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	N
E/T	0.8827	likely_pathogenic	0.8996	pathogenic	-0.993	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
E/V	0.8634	likely_pathogenic	0.8828	pathogenic	-0.146	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
E/W	0.9977	likely_pathogenic	0.9982	pathogenic	0.34	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/Y	0.9873	likely_pathogenic	0.9897	pathogenic	0.276	Stabilizing	1.0	D	0.829	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.