TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26582	79969;79970;79971	chr2:178566388;178566387;178566386	chr2:179431115;179431114;179431113
N2AB	24941	75046;75047;75048	chr2:178566388;178566387;178566386	chr2:179431115;179431114;179431113
N2A	24014	72265;72266;72267	chr2:178566388;178566387;178566386	chr2:179431115;179431114;179431113
N2B	17517	52774;52775;52776	chr2:178566388;178566387;178566386	chr2:179431115;179431114;179431113
Novex-1	17642	53149;53150;53151	chr2:178566388;178566387;178566386	chr2:179431115;179431114;179431113
Novex-2	17709	53350;53351;53352	chr2:178566388;178566387;178566386	chr2:179431115;179431114;179431113
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: Fn3-81
• Domain position: 96
• Structural Position: 129
• Q(SASA): 0.4546
• 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/Q	rs775918922	-0.427	0.931	N	0.641	0.307	0.345859378078	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	1.15908E-04	None	0	0	None	0	None	0	0	0
K/Q	rs775918922	-0.427	0.931	N	0.641	0.307	0.345859378078	gnomAD-4.0.0	6.36736E-06	None	None	None	None	N	None	0	9.14578E-05	None	0	0	None	0	0	0	0	0
K/T	None	None	0.964	N	0.612	0.382	0.45783149361	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-06	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	0.4627	ambiguous	0.3896	ambiguous	-0.698	Destabilizing	0.835	D	0.605	neutral	None	None	None	None	N
K/C	0.5779	likely_pathogenic	0.5293	ambiguous	-0.802	Destabilizing	0.998	D	0.77	deleterious	None	None	None	None	N
K/D	0.8837	likely_pathogenic	0.8357	pathogenic	-0.618	Destabilizing	0.947	D	0.63	neutral	None	None	None	None	N
K/E	0.3553	ambiguous	0.288	benign	-0.45	Destabilizing	0.792	D	0.499	neutral	N	0.497061459	None	None	N
K/F	0.6921	likely_pathogenic	0.6234	pathogenic	-0.087	Destabilizing	0.973	D	0.803	deleterious	None	None	None	None	N
K/G	0.7025	likely_pathogenic	0.6311	pathogenic	-1.129	Destabilizing	0.947	D	0.573	neutral	None	None	None	None	N
K/H	0.3784	ambiguous	0.331	benign	-1.421	Destabilizing	0.035	N	0.541	neutral	None	None	None	None	N
K/I	0.2158	likely_benign	0.1855	benign	0.453	Stabilizing	0.964	D	0.812	deleterious	N	0.446558067	None	None	N
K/L	0.3042	likely_benign	0.2586	benign	0.453	Stabilizing	0.947	D	0.566	neutral	None	None	None	None	N
K/M	0.1861	likely_benign	0.1602	benign	0.209	Stabilizing	0.998	D	0.733	deleterious	None	None	None	None	N
K/N	0.6438	likely_pathogenic	0.5491	ambiguous	-0.977	Destabilizing	0.931	D	0.633	neutral	N	0.511492193	None	None	N
K/P	0.8572	likely_pathogenic	0.8199	pathogenic	0.099	Stabilizing	0.991	D	0.727	deleterious	None	None	None	None	N
K/Q	0.1627	likely_benign	0.1436	benign	-0.901	Destabilizing	0.931	D	0.641	neutral	N	0.478128981	None	None	N
K/R	0.0936	likely_benign	0.0896	benign	-0.955	Destabilizing	0.792	D	0.569	neutral	N	0.491519566	None	None	N
K/S	0.5892	likely_pathogenic	0.497	ambiguous	-1.553	Destabilizing	0.835	D	0.619	neutral	None	None	None	None	N
K/T	0.2138	likely_benign	0.1708	benign	-1.164	Destabilizing	0.964	D	0.612	neutral	N	0.437687868	None	None	N
K/V	0.2431	likely_benign	0.2139	benign	0.099	Stabilizing	0.973	D	0.733	deleterious	None	None	None	None	N
K/W	0.7675	likely_pathogenic	0.7376	pathogenic	-0.034	Destabilizing	0.998	D	0.725	deleterious	None	None	None	None	N
K/Y	0.6075	likely_pathogenic	0.5651	pathogenic	0.252	Stabilizing	0.899	D	0.787	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.