TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27186	81781;81782;81783	chr2:178564576;178564575;178564574	chr2:179429303;179429302;179429301
N2AB	25545	76858;76859;76860	chr2:178564576;178564575;178564574	chr2:179429303;179429302;179429301
N2A	24618	74077;74078;74079	chr2:178564576;178564575;178564574	chr2:179429303;179429302;179429301
N2B	18121	54586;54587;54588	chr2:178564576;178564575;178564574	chr2:179429303;179429302;179429301
Novex-1	18246	54961;54962;54963	chr2:178564576;178564575;178564574	chr2:179429303;179429302;179429301
Novex-2	18313	55162;55163;55164	chr2:178564576;178564575;178564574	chr2:179429303;179429302;179429301
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-86
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.2295
• 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
N/K	None	None	0.012	N	0.314	0.074	0.0401082797425	gnomAD-4.0.0	2.05308E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69861E-06	0	0
N/S	rs368933290	None	None	N	0.061	0.132	None	gnomAD-4.0.0	1.59208E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85901E-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
N/A	0.1256	likely_benign	0.1175	benign	-0.519	Destabilizing	0.007	N	0.33	neutral	None	None	None	None	N
N/C	0.1024	likely_benign	0.0963	benign	-0.275	Destabilizing	0.356	N	0.583	neutral	None	None	None	None	N
N/D	0.1131	likely_benign	0.1023	benign	-1.787	Destabilizing	0.012	N	0.329	neutral	N	0.465743182	None	None	N
N/E	0.2815	likely_benign	0.2455	benign	-1.699	Destabilizing	0.016	N	0.303	neutral	None	None	None	None	N
N/F	0.2476	likely_benign	0.2074	benign	-0.692	Destabilizing	None	N	0.396	neutral	None	None	None	None	N
N/G	0.1995	likely_benign	0.1961	benign	-0.792	Destabilizing	0.016	N	0.263	neutral	None	None	None	None	N
N/H	0.0664	likely_benign	0.0644	benign	-0.692	Destabilizing	None	N	0.107	neutral	N	0.406100233	None	None	N
N/I	0.1581	likely_benign	0.1346	benign	0.148	Stabilizing	0.029	N	0.517	neutral	N	0.500549189	None	None	N
N/K	0.2584	likely_benign	0.2214	benign	-0.129	Destabilizing	0.012	N	0.314	neutral	N	0.46935949	None	None	N
N/L	0.1503	likely_benign	0.1292	benign	0.148	Stabilizing	None	N	0.359	neutral	None	None	None	None	N
N/M	0.1802	likely_benign	0.1643	benign	0.614	Stabilizing	0.214	N	0.592	neutral	None	None	None	None	N
N/P	0.9524	likely_pathogenic	0.9304	pathogenic	-0.047	Destabilizing	0.072	N	0.615	neutral	None	None	None	None	N
N/Q	0.1968	likely_benign	0.1792	benign	-1.151	Destabilizing	0.072	N	0.406	neutral	None	None	None	None	N
N/R	0.2669	likely_benign	0.2333	benign	0.018	Stabilizing	0.072	N	0.389	neutral	None	None	None	None	N
N/S	0.0513	likely_benign	0.0517	benign	-0.82	Destabilizing	None	N	0.061	neutral	N	0.285899109	None	None	N
N/T	0.0664	likely_benign	0.0635	benign	-0.58	Destabilizing	0.012	N	0.295	neutral	N	0.353764471	None	None	N
N/V	0.1562	likely_benign	0.1364	benign	-0.047	Destabilizing	0.016	N	0.416	neutral	None	None	None	None	N
N/W	0.5486	ambiguous	0.4895	ambiguous	-0.607	Destabilizing	0.356	N	0.579	neutral	None	None	None	None	N
N/Y	0.0941	likely_benign	0.0741	benign	-0.22	Destabilizing	None	N	0.326	neutral	N	0.408273746	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.