TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25764	77515;77516;77517	chr2:178568842;178568841;178568840	chr2:179433569;179433568;179433567
N2AB	24123	72592;72593;72594	chr2:178568842;178568841;178568840	chr2:179433569;179433568;179433567
N2A	23196	69811;69812;69813	chr2:178568842;178568841;178568840	chr2:179433569;179433568;179433567
N2B	16699	50320;50321;50322	chr2:178568842;178568841;178568840	chr2:179433569;179433568;179433567
Novex-1	16824	50695;50696;50697	chr2:178568842;178568841;178568840	chr2:179433569;179433568;179433567
Novex-2	16891	50896;50897;50898	chr2:178568842;178568841;178568840	chr2:179433569;179433568;179433567
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Fn3-75
• Domain position: 67
• Structural Position: 100
• Q(SASA): 0.3019
• 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
G/R	None	None	0.704	D	0.647	0.54	0.610263417295	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.93349E-04	None	0	0	0	0	0
G/R	None	None	0.704	D	0.647	0.54	0.610263417295	gnomAD-4.0.0	2.05348E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79925E-06	0	1.65722E-05

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
G/A	0.4578	ambiguous	0.4595	ambiguous	-0.534	Destabilizing	0.962	D	0.655	neutral	N	0.488229862	None	None	N
G/C	0.6208	likely_pathogenic	0.6188	pathogenic	-0.918	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
G/D	0.3456	ambiguous	0.3412	ambiguous	-0.949	Destabilizing	0.998	D	0.797	deleterious	None	None	None	None	N
G/E	0.4798	ambiguous	0.4763	ambiguous	-1.101	Destabilizing	0.998	D	0.837	deleterious	N	0.497117405	None	None	N
G/F	0.8965	likely_pathogenic	0.8944	pathogenic	-1.139	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
G/H	0.7347	likely_pathogenic	0.7291	pathogenic	-0.843	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
G/I	0.9049	likely_pathogenic	0.9123	pathogenic	-0.547	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
G/K	0.8133	likely_pathogenic	0.8155	pathogenic	-1.134	Destabilizing	0.997	D	0.841	deleterious	None	None	None	None	N
G/L	0.8339	likely_pathogenic	0.8323	pathogenic	-0.547	Destabilizing	0.998	D	0.857	deleterious	None	None	None	None	N
G/M	0.8341	likely_pathogenic	0.8259	pathogenic	-0.461	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
G/N	0.3375	likely_benign	0.3216	benign	-0.726	Destabilizing	0.998	D	0.817	deleterious	None	None	None	None	N
G/P	0.9931	likely_pathogenic	0.9936	pathogenic	-0.507	Destabilizing	0.999	D	0.873	deleterious	None	None	None	None	N
G/Q	0.6482	likely_pathogenic	0.6441	pathogenic	-1.043	Destabilizing	0.998	D	0.873	deleterious	None	None	None	None	N
G/R	0.7403	likely_pathogenic	0.7469	pathogenic	-0.624	Destabilizing	0.704	D	0.647	neutral	D	0.52519884	None	None	N
G/S	0.25	likely_benign	0.2444	benign	-0.876	Destabilizing	0.991	D	0.796	deleterious	None	None	None	None	N
G/T	0.5635	ambiguous	0.5641	pathogenic	-0.966	Destabilizing	0.998	D	0.857	deleterious	None	None	None	None	N
G/V	0.8031	likely_pathogenic	0.8192	pathogenic	-0.507	Destabilizing	0.999	D	0.857	deleterious	D	0.525959309	None	None	N
G/W	0.769	likely_pathogenic	0.7639	pathogenic	-1.311	Destabilizing	1.0	D	0.854	deleterious	N	0.48992861	None	None	N
G/Y	0.7645	likely_pathogenic	0.7575	pathogenic	-0.978	Destabilizing	1.0	D	0.853	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.