TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6542	19849;19850;19851	chr2:178728200;178728199;178728198	chr2:179592927;179592926;179592925
N2AB	6225	18898;18899;18900	chr2:178728200;178728199;178728198	chr2:179592927;179592926;179592925
N2A	5298	16117;16118;16119	chr2:178728200;178728199;178728198	chr2:179592927;179592926;179592925
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-49
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.3888
• 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	rs374003118	None	0.042	N	0.305	0.111	0.0297737177859	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	6.48E-05	0	None	0	0	None	0	None	0	0	0
N/Y	rs750316803	-0.418	0.602	N	0.478	0.257	0.415820034956	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
N/Y	rs750316803	-0.418	0.602	N	0.478	0.257	0.415820034956	gnomAD-4.0.0	1.59365E-06	None	None	None	None	N	None	0	0	None	0	2.77901E-05	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
N/A	0.1741	likely_benign	0.2147	benign	-0.575	Destabilizing	0.055	N	0.403	neutral	None	None	None	None	N
N/C	0.2411	likely_benign	0.2974	benign	0.273	Stabilizing	0.002	N	0.345	neutral	None	None	None	None	N
N/D	0.0956	likely_benign	0.111	benign	-0.291	Destabilizing	0.081	N	0.323	neutral	N	0.453746959	None	None	N
N/E	0.2545	likely_benign	0.3085	benign	-0.299	Destabilizing	0.055	N	0.313	neutral	None	None	None	None	N
N/F	0.3837	ambiguous	0.4581	ambiguous	-0.847	Destabilizing	0.497	N	0.497	neutral	None	None	None	None	N
N/G	0.209	likely_benign	0.2639	benign	-0.788	Destabilizing	0.104	N	0.312	neutral	None	None	None	None	N
N/H	0.075	likely_benign	0.0787	benign	-0.814	Destabilizing	0.602	D	0.396	neutral	N	0.513720769	None	None	N
N/I	0.2146	likely_benign	0.2506	benign	-0.086	Destabilizing	0.001	N	0.328	neutral	N	0.503567007	None	None	N
N/K	0.1749	likely_benign	0.21	benign	0.035	Stabilizing	0.042	N	0.305	neutral	N	0.464945387	None	None	N
N/L	0.1955	likely_benign	0.231	benign	-0.086	Destabilizing	0.02	N	0.453	neutral	None	None	None	None	N
N/M	0.2924	likely_benign	0.3511	ambiguous	0.547	Stabilizing	0.497	N	0.469	neutral	None	None	None	None	N
N/P	0.6322	likely_pathogenic	0.6555	pathogenic	-0.222	Destabilizing	0.667	D	0.501	neutral	None	None	None	None	N
N/Q	0.1916	likely_benign	0.2331	benign	-0.625	Destabilizing	0.005	N	0.108	neutral	None	None	None	None	N
N/R	0.1785	likely_benign	0.2089	benign	0.146	Stabilizing	0.22	N	0.325	neutral	None	None	None	None	N
N/S	0.0812	likely_benign	0.0909	benign	-0.362	Destabilizing	0.008	N	0.117	neutral	N	0.464772029	None	None	N
N/T	0.1279	likely_benign	0.1495	benign	-0.213	Destabilizing	0.001	N	0.111	neutral	N	0.49001719	None	None	N
N/V	0.2073	likely_benign	0.2501	benign	-0.222	Destabilizing	0.02	N	0.453	neutral	None	None	None	None	N
N/W	0.658	likely_pathogenic	0.7378	pathogenic	-0.716	Destabilizing	0.958	D	0.477	neutral	None	None	None	None	N
N/Y	0.1304	likely_benign	0.145	benign	-0.472	Destabilizing	0.602	D	0.478	neutral	N	0.491703722	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.