TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32603	98032;98033;98034	chr2:178540359;178540358;178540357	chr2:179405086;179405085;179405084
N2AB	30962	93109;93110;93111	chr2:178540359;178540358;178540357	chr2:179405086;179405085;179405084
N2A	30035	90328;90329;90330	chr2:178540359;178540358;178540357	chr2:179405086;179405085;179405084
N2B	23538	70837;70838;70839	chr2:178540359;178540358;178540357	chr2:179405086;179405085;179405084
Novex-1	23663	71212;71213;71214	chr2:178540359;178540358;178540357	chr2:179405086;179405085;179405084
Novex-2	23730	71413;71414;71415	chr2:178540359;178540358;178540357	chr2:179405086;179405085;179405084
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: Fn3-126
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.3852
• 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	rs778929590	-0.414	0.006	N	0.348	0.052	0.184867976434	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.66945E-04
K/R	rs778929590	-0.414	0.006	N	0.348	0.052	0.184867976434	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	0	4.77555E-04
K/R	rs778929590	-0.414	0.006	N	0.348	0.052	0.184867976434	gnomAD-4.0.0	6.57047E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	4.77555E-04

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	0.2534	likely_benign	0.2824	benign	-0.388	Destabilizing	0.013	N	0.375	neutral	None	None	None	None	N
K/C	0.4858	ambiguous	0.4844	ambiguous	-0.405	Destabilizing	0.995	D	0.65	neutral	None	None	None	None	N
K/D	0.6599	likely_pathogenic	0.6809	pathogenic	-0.18	Destabilizing	0.828	D	0.597	neutral	None	None	None	None	N
K/E	0.2133	likely_benign	0.2431	benign	-0.094	Destabilizing	0.642	D	0.517	neutral	N	0.456662339	None	None	N
K/F	0.6829	likely_pathogenic	0.695	pathogenic	-0.077	Destabilizing	0.944	D	0.683	prob.neutral	None	None	None	None	N
K/G	0.4621	ambiguous	0.495	ambiguous	-0.74	Destabilizing	0.704	D	0.62	neutral	None	None	None	None	N
K/H	0.343	ambiguous	0.3548	ambiguous	-1.116	Destabilizing	0.944	D	0.593	neutral	None	None	None	None	N
K/I	0.2416	likely_benign	0.251	benign	0.515	Stabilizing	0.031	N	0.53	neutral	None	None	None	None	N
K/L	0.2932	likely_benign	0.302	benign	0.515	Stabilizing	0.329	N	0.575	neutral	None	None	None	None	N
K/M	0.188	likely_benign	0.2037	benign	0.379	Stabilizing	0.927	D	0.589	neutral	N	0.501936056	None	None	N
K/N	0.4388	ambiguous	0.4673	ambiguous	-0.346	Destabilizing	0.642	D	0.524	neutral	N	0.501069264	None	None	N
K/P	0.2509	likely_benign	0.2453	benign	0.245	Stabilizing	0.003	N	0.365	neutral	None	None	None	None	N
K/Q	0.1394	likely_benign	0.149	benign	-0.448	Destabilizing	0.642	D	0.52	neutral	N	0.441116883	None	None	N
K/R	0.0906	likely_benign	0.0925	benign	-0.628	Destabilizing	0.006	N	0.348	neutral	N	0.448197571	None	None	N
K/S	0.3606	ambiguous	0.4057	ambiguous	-0.927	Destabilizing	0.329	N	0.499	neutral	None	None	None	None	N
K/T	0.1992	likely_benign	0.2229	benign	-0.649	Destabilizing	0.642	D	0.597	neutral	N	0.445215981	None	None	N
K/V	0.2447	likely_benign	0.2532	benign	0.245	Stabilizing	0.329	N	0.584	neutral	None	None	None	None	N
K/W	0.7643	likely_pathogenic	0.783	pathogenic	0.024	Stabilizing	0.995	D	0.656	neutral	None	None	None	None	N
K/Y	0.5433	ambiguous	0.5513	ambiguous	0.3	Stabilizing	0.981	D	0.674	neutral	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.