TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20266	61021;61022;61023	chr2:178590929;178590928;178590927	chr2:179455656;179455655;179455654
N2AB	18625	56098;56099;56100	chr2:178590929;178590928;178590927	chr2:179455656;179455655;179455654
N2A	17698	53317;53318;53319	chr2:178590929;178590928;178590927	chr2:179455656;179455655;179455654
N2B	11201	33826;33827;33828	chr2:178590929;178590928;178590927	chr2:179455656;179455655;179455654
Novex-1	11326	34201;34202;34203	chr2:178590929;178590928;178590927	chr2:179455656;179455655;179455654
Novex-2	11393	34402;34403;34404	chr2:178590929;178590928;178590927	chr2:179455656;179455655;179455654
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-34
• Domain position: 96
• Structural Position: 131
• Q(SASA): 0.0414
• 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/E	rs763212024	-1.98	0.06	N	0.143	0.142	None	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	1.29282E-04	5.8E-05	None	0	0	None	0	None	0	0	0
K/E	rs763212024	-1.98	0.06	N	0.143	0.142	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	9.65E-05	0	0	0	0	None	0	0	0	0	0
K/E	rs763212024	-1.98	0.06	N	0.143	0.142	None	gnomAD-4.0.0	6.81953E-06	None	None	None	None	N	None	1.06846E-04	3.33578E-05	None	0	0	None	0	0	8.47923E-07	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
K/A	0.311	likely_benign	0.2964	benign	-0.192	Destabilizing	0.938	D	0.643	neutral	None	None	None	None	N
K/C	0.4931	ambiguous	0.4758	ambiguous	-0.337	Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
K/D	0.6769	likely_pathogenic	0.651	pathogenic	-0.015	Destabilizing	0.883	D	0.666	prob.neutral	None	None	None	None	N
K/E	0.1488	likely_benign	0.1496	benign	0.068	Stabilizing	0.06	N	0.143	neutral	N	0.507741733	None	None	N
K/F	0.7323	likely_pathogenic	0.6924	pathogenic	0.03	Stabilizing	0.997	D	0.775	deleterious	None	None	None	None	N
K/G	0.4952	ambiguous	0.4875	ambiguous	-0.503	Destabilizing	0.968	D	0.663	prob.neutral	None	None	None	None	N
K/H	0.3096	likely_benign	0.2854	benign	-0.708	Destabilizing	0.997	D	0.674	prob.neutral	None	None	None	None	N
K/I	0.275	likely_benign	0.257	benign	0.586	Stabilizing	0.997	D	0.786	deleterious	None	None	None	None	N
K/L	0.3163	likely_benign	0.304	benign	0.586	Stabilizing	0.938	D	0.667	prob.neutral	None	None	None	None	N
K/M	0.183	likely_benign	0.1754	benign	0.169	Stabilizing	0.999	D	0.672	prob.neutral	N	0.48131583	None	None	N
K/N	0.4835	ambiguous	0.4624	ambiguous	-0.132	Destabilizing	0.958	D	0.66	prob.neutral	N	0.492925625	None	None	N
K/P	0.9373	likely_pathogenic	0.9348	pathogenic	0.356	Stabilizing	0.997	D	0.676	prob.neutral	None	None	None	None	N
K/Q	0.1007	likely_benign	0.0978	benign	-0.168	Destabilizing	0.919	D	0.637	neutral	N	0.509299171	None	None	N
K/R	0.078	likely_benign	0.0792	benign	-0.32	Destabilizing	0.034	N	0.279	neutral	N	0.466180325	None	None	N
K/S	0.3705	ambiguous	0.346	ambiguous	-0.634	Destabilizing	0.938	D	0.583	neutral	None	None	None	None	N
K/T	0.1494	likely_benign	0.1402	benign	-0.366	Destabilizing	0.958	D	0.685	prob.delet.	N	0.516646431	None	None	N
K/V	0.2123	likely_benign	0.198	benign	0.356	Stabilizing	0.991	D	0.659	prob.neutral	None	None	None	None	N
K/W	0.7524	likely_pathogenic	0.7211	pathogenic	0.049	Stabilizing	0.999	D	0.78	deleterious	None	None	None	None	N
K/Y	0.6159	likely_pathogenic	0.5927	pathogenic	0.339	Stabilizing	0.997	D	0.717	prob.delet.	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.