TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6554	19885;19886;19887	chr2:178728164;178728163;178728162	chr2:179592891;179592890;179592889
N2AB	6237	18934;18935;18936	chr2:178728164;178728163;178728162	chr2:179592891;179592890;179592889
N2A	5310	16153;16154;16155	chr2:178728164;178728163;178728162	chr2:179592891;179592890;179592889
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-49
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.2887
• 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
K/R	rs2079687407	None	0.002	N	0.375	0.084	0.211220785272	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07383E-04	0
K/R	rs2079687407	None	0.002	N	0.375	0.084	0.211220785272	gnomAD-4.0.0	1.86322E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.69811E-06	1.10468E-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
K/A	0.3672	ambiguous	0.3978	ambiguous	-0.919	Destabilizing	0.157	N	0.637	neutral	None	None	None	None	N
K/C	0.6349	likely_pathogenic	0.6712	pathogenic	-0.998	Destabilizing	0.968	D	0.737	prob.delet.	None	None	None	None	N
K/D	0.6946	likely_pathogenic	0.7287	pathogenic	-0.62	Destabilizing	0.157	N	0.674	neutral	None	None	None	None	N
K/E	0.1899	likely_benign	0.2155	benign	-0.465	Destabilizing	0.124	N	0.577	neutral	N	0.482342722	None	None	N
K/F	0.6905	likely_pathogenic	0.7219	pathogenic	-0.526	Destabilizing	0.726	D	0.755	deleterious	None	None	None	None	N
K/G	0.5714	likely_pathogenic	0.6029	pathogenic	-1.329	Destabilizing	0.157	N	0.707	prob.neutral	None	None	None	None	N
K/H	0.2462	likely_benign	0.259	benign	-1.674	Destabilizing	0.726	D	0.713	prob.delet.	None	None	None	None	N
K/I	0.2509	likely_benign	0.2706	benign	0.171	Stabilizing	0.667	D	0.757	deleterious	N	0.435167638	None	None	N
K/L	0.3135	likely_benign	0.3369	benign	0.171	Stabilizing	0.272	N	0.747	deleterious	None	None	None	None	N
K/M	0.1875	likely_benign	0.2108	benign	0.086	Stabilizing	0.968	D	0.695	prob.neutral	None	None	None	None	N
K/N	0.4166	ambiguous	0.4615	ambiguous	-0.92	Destabilizing	0.001	N	0.389	neutral	D	0.532232825	None	None	N
K/P	0.9686	likely_pathogenic	0.9726	pathogenic	-0.163	Destabilizing	0.726	D	0.733	prob.delet.	None	None	None	None	N
K/Q	0.1248	likely_benign	0.1327	benign	-0.94	Destabilizing	0.497	N	0.625	neutral	N	0.496290667	None	None	N
K/R	0.0735	likely_benign	0.0723	benign	-0.859	Destabilizing	0.002	N	0.375	neutral	N	0.466181191	None	None	N
K/S	0.3717	ambiguous	0.4144	ambiguous	-1.603	Destabilizing	0.005	N	0.391	neutral	None	None	None	None	N
K/T	0.1398	likely_benign	0.1576	benign	-1.22	Destabilizing	0.124	N	0.657	neutral	N	0.472933805	None	None	N
K/V	0.2528	likely_benign	0.2653	benign	-0.163	Destabilizing	0.567	D	0.743	deleterious	None	None	None	None	N
K/W	0.6919	likely_pathogenic	0.7151	pathogenic	-0.398	Destabilizing	0.968	D	0.687	prob.neutral	None	None	None	None	N
K/Y	0.562	ambiguous	0.589	pathogenic	-0.084	Destabilizing	0.726	D	0.764	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.