TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17914	53965;53966;53967	chr2:178605555;178605554;178605553	chr2:179470282;179470281;179470280
N2AB	16273	49042;49043;49044	chr2:178605555;178605554;178605553	chr2:179470282;179470281;179470280
N2A	15346	46261;46262;46263	chr2:178605555;178605554;178605553	chr2:179470282;179470281;179470280
N2B	8849	26770;26771;26772	chr2:178605555;178605554;178605553	chr2:179470282;179470281;179470280
Novex-1	8974	27145;27146;27147	chr2:178605555;178605554;178605553	chr2:179470282;179470281;179470280
Novex-2	9041	27346;27347;27348	chr2:178605555;178605554;178605553	chr2:179470282;179470281;179470280
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: Fn3-18
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.6868
• 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/T	None	None	None	N	0.17	0.114	0.0551355673512	gnomAD-4.0.0	2.76429E-06	None	None	None	None	N	None	0	0	None	0	2.56753E-05	None	1.98523E-05	0	1.81267E-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	0.1665	likely_benign	0.2029	benign	0.054	Stabilizing	None	N	0.157	neutral	None	None	None	None	N
K/C	0.5342	ambiguous	0.5976	pathogenic	-0.333	Destabilizing	0.676	D	0.237	neutral	None	None	None	None	N
K/D	0.2049	likely_benign	0.244	benign	-0.151	Destabilizing	0.072	N	0.382	neutral	None	None	None	None	N
K/E	0.0965	likely_benign	0.1068	benign	-0.163	Destabilizing	0.012	N	0.329	neutral	N	0.456584981	None	None	N
K/F	0.6039	likely_pathogenic	0.6533	pathogenic	-0.276	Destabilizing	0.356	N	0.278	neutral	None	None	None	None	N
K/G	0.1912	likely_benign	0.2297	benign	-0.082	Destabilizing	0.016	N	0.341	neutral	None	None	None	None	N
K/H	0.1995	likely_benign	0.2207	benign	-0.216	Destabilizing	0.214	N	0.274	neutral	None	None	None	None	N
K/I	0.296	likely_benign	0.3361	benign	0.329	Stabilizing	0.214	N	0.345	neutral	None	None	None	None	N
K/L	0.2448	likely_benign	0.2774	benign	0.329	Stabilizing	0.016	N	0.357	neutral	None	None	None	None	N
K/M	0.2081	likely_benign	0.2342	benign	0.006	Stabilizing	0.295	N	0.275	neutral	N	0.518404231	None	None	N
K/N	0.1916	likely_benign	0.2178	benign	0.139	Stabilizing	0.055	N	0.31	neutral	N	0.502069341	None	None	N
K/P	0.2436	likely_benign	0.2281	benign	0.261	Stabilizing	None	N	0.172	neutral	None	None	None	None	N
K/Q	0.09	likely_benign	0.0996	benign	-0.01	Destabilizing	None	N	0.225	neutral	N	0.484000869	None	None	N
K/R	0.081	likely_benign	0.0868	benign	-0.03	Destabilizing	0.029	N	0.334	neutral	N	0.431899967	None	None	N
K/S	0.1707	likely_benign	0.1961	benign	-0.251	Destabilizing	0.016	N	0.302	neutral	None	None	None	None	N
K/T	0.1056	likely_benign	0.1129	benign	-0.142	Destabilizing	None	N	0.17	neutral	N	0.428822377	None	None	N
K/V	0.2377	likely_benign	0.2722	benign	0.261	Stabilizing	0.038	N	0.355	neutral	None	None	None	None	N
K/W	0.6002	likely_pathogenic	0.6466	pathogenic	-0.37	Destabilizing	0.864	D	0.239	neutral	None	None	None	None	N
K/Y	0.4423	ambiguous	0.4946	ambiguous	-0.01	Destabilizing	0.356	N	0.293	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.