TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6292	19099;19100;19101	chr2:178729164;178729163;178729162	chr2:179593891;179593890;179593889
N2AB	5975	18148;18149;18150	chr2:178729164;178729163;178729162	chr2:179593891;179593890;179593889
N2A	5048	15367;15368;15369	chr2:178729164;178729163;178729162	chr2:179593891;179593890;179593889
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: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-47
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.1931
• 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	rs1180688317	-1.925	0.987	D	0.834	0.765	0.633965432156	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
P/S	rs1180688317	-1.925	0.987	D	0.834	0.765	0.633965432156	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
P/S	rs1180688317	-1.925	0.987	D	0.834	0.765	0.633965432156	gnomAD-4.0.0	6.57436E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47059E-05	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	0.4285	ambiguous	0.4113	ambiguous	-1.614	Destabilizing	0.117	N	0.693	prob.neutral	D	0.615619841	None	None	N
P/C	0.9606	likely_pathogenic	0.9609	pathogenic	-1.386	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
P/D	0.9989	likely_pathogenic	0.9988	pathogenic	-1.4	Destabilizing	0.998	D	0.888	deleterious	None	None	None	None	N
P/E	0.9955	likely_pathogenic	0.9947	pathogenic	-1.382	Destabilizing	0.995	D	0.889	deleterious	None	None	None	None	N
P/F	0.9968	likely_pathogenic	0.9969	pathogenic	-1.301	Destabilizing	0.999	D	0.888	deleterious	None	None	None	None	N
P/G	0.978	likely_pathogenic	0.9778	pathogenic	-1.938	Destabilizing	0.966	D	0.835	deleterious	None	None	None	None	N
P/H	0.9935	likely_pathogenic	0.9937	pathogenic	-1.415	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
P/I	0.9114	likely_pathogenic	0.8888	pathogenic	-0.814	Destabilizing	0.995	D	0.882	deleterious	None	None	None	None	N
P/K	0.997	likely_pathogenic	0.997	pathogenic	-1.181	Destabilizing	0.995	D	0.888	deleterious	None	None	None	None	N
P/L	0.8332	likely_pathogenic	0.8138	pathogenic	-0.814	Destabilizing	0.993	D	0.866	deleterious	D	0.657580923	None	None	N
P/M	0.9786	likely_pathogenic	0.9757	pathogenic	-0.804	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
P/N	0.997	likely_pathogenic	0.9969	pathogenic	-1.057	Destabilizing	0.998	D	0.881	deleterious	None	None	None	None	N
P/Q	0.9881	likely_pathogenic	0.9878	pathogenic	-1.233	Destabilizing	0.997	D	0.883	deleterious	D	0.657782727	None	None	N
P/R	0.9868	likely_pathogenic	0.9867	pathogenic	-0.733	Destabilizing	0.997	D	0.883	deleterious	D	0.657782727	None	None	N
P/S	0.9298	likely_pathogenic	0.9255	pathogenic	-1.655	Destabilizing	0.987	D	0.834	deleterious	D	0.641359757	None	None	N
P/T	0.8921	likely_pathogenic	0.8762	pathogenic	-1.523	Destabilizing	0.993	D	0.878	deleterious	D	0.657580923	None	None	N
P/V	0.7593	likely_pathogenic	0.7117	pathogenic	-1.047	Destabilizing	0.99	D	0.858	deleterious	None	None	None	None	N
P/W	0.9994	likely_pathogenic	0.9994	pathogenic	-1.442	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
P/Y	0.9979	likely_pathogenic	0.9981	pathogenic	-1.134	Destabilizing	1.0	D	0.889	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.