TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27036	81331;81332;81333	chr2:178565026;178565025;178565024	chr2:179429753;179429752;179429751
N2AB	25395	76408;76409;76410	chr2:178565026;178565025;178565024	chr2:179429753;179429752;179429751
N2A	24468	73627;73628;73629	chr2:178565026;178565025;178565024	chr2:179429753;179429752;179429751
N2B	17971	54136;54137;54138	chr2:178565026;178565025;178565024	chr2:179429753;179429752;179429751
Novex-1	18096	54511;54512;54513	chr2:178565026;178565025;178565024	chr2:179429753;179429752;179429751
Novex-2	18163	54712;54713;54714	chr2:178565026;178565025;178565024	chr2:179429753;179429752;179429751
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: Fn3-84
• Domain position: 65
• Structural Position: 96
• Q(SASA): 0.8392
• 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	rs545554093	0.111	0.822	N	0.484	0.256	0.269558022972	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	0	0	0
K/E	rs545554093	0.111	0.822	N	0.484	0.256	0.269558022972	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.93723E-04	None	0	0	0	0	0
K/E	rs545554093	0.111	0.822	N	0.484	0.256	0.269558022972	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	1E-03	0	None	None	None	0	None
K/E	rs545554093	0.111	0.822	N	0.484	0.256	0.269558022972	gnomAD-4.0.0	2.0297E-06	None	None	None	None	N	None	0	0	None	0	2.2779E-04	None	0	0	0	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	0.5662	likely_pathogenic	0.5754	pathogenic	0.049	Stabilizing	0.86	D	0.516	neutral	None	None	None	None	N
K/C	0.7709	likely_pathogenic	0.7552	pathogenic	-0.313	Destabilizing	0.998	D	0.649	neutral	None	None	None	None	N
K/D	0.7459	likely_pathogenic	0.7546	pathogenic	-0.186	Destabilizing	0.754	D	0.517	neutral	None	None	None	None	N
K/E	0.5548	ambiguous	0.5754	pathogenic	-0.191	Destabilizing	0.822	D	0.484	neutral	N	0.507875019	None	None	N
K/F	0.9395	likely_pathogenic	0.9355	pathogenic	-0.227	Destabilizing	0.978	D	0.613	neutral	None	None	None	None	N
K/G	0.4572	ambiguous	0.5004	ambiguous	-0.107	Destabilizing	0.86	D	0.515	neutral	None	None	None	None	N
K/H	0.31	likely_benign	0.2852	benign	-0.231	Destabilizing	0.043	N	0.505	neutral	None	None	None	None	N
K/I	0.83	likely_pathogenic	0.8266	pathogenic	0.379	Stabilizing	0.97	D	0.602	neutral	N	0.500990248	None	None	N
K/L	0.7155	likely_pathogenic	0.7009	pathogenic	0.379	Stabilizing	0.86	D	0.519	neutral	None	None	None	None	N
K/M	0.6141	likely_pathogenic	0.6155	pathogenic	0.028	Stabilizing	0.998	D	0.525	neutral	None	None	None	None	N
K/N	0.5222	ambiguous	0.5376	ambiguous	0.136	Stabilizing	0.058	N	0.312	neutral	N	0.409305535	None	None	N
K/P	0.8502	likely_pathogenic	0.8546	pathogenic	0.294	Stabilizing	0.993	D	0.527	neutral	None	None	None	None	N
K/Q	0.2537	likely_benign	0.2475	benign	-0.018	Destabilizing	0.942	D	0.531	neutral	N	0.473224755	None	None	N
K/R	0.0784	likely_benign	0.0775	benign	-0.022	Destabilizing	0.014	N	0.266	neutral	N	0.437919076	None	None	N
K/S	0.5739	likely_pathogenic	0.5859	pathogenic	-0.257	Destabilizing	0.86	D	0.475	neutral	None	None	None	None	N
K/T	0.4688	ambiguous	0.4725	ambiguous	-0.135	Destabilizing	0.822	D	0.515	neutral	N	0.482036619	None	None	N
K/V	0.7454	likely_pathogenic	0.7344	pathogenic	0.294	Stabilizing	0.978	D	0.538	neutral	None	None	None	None	N
K/W	0.8949	likely_pathogenic	0.8891	pathogenic	-0.308	Destabilizing	0.998	D	0.689	prob.neutral	None	None	None	None	N
K/Y	0.7845	likely_pathogenic	0.7755	pathogenic	0.046	Stabilizing	0.915	D	0.571	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.