TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6938	21037;21038;21039	chr2:178725392;178725391;178725390	chr2:179590119;179590118;179590117
N2AB	6621	20086;20087;20088	chr2:178725392;178725391;178725390	chr2:179590119;179590118;179590117
N2A	5694	17305;17306;17307	chr2:178725392;178725391;178725390	chr2:179590119;179590118;179590117
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: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-53
• Domain position: 85
• Structural Position: 169
• Q(SASA): 0.1553
• 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/D	None	None	0.081	N	0.444	0.128	0.201204373187	gnomAD-4.0.0	1.65252E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.53827E-05	0
N/Y	rs769865946	0.055	0.602	N	0.611	0.275	0.609517086792	gnomAD-2.1.1	4.46E-06	None	None	None	None	N	None	6.85E-05	0	None	0	0	None	0	None	0	0	0
N/Y	rs769865946	0.055	0.602	N	0.611	0.275	0.609517086792	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
N/Y	rs769865946	0.055	0.602	N	0.611	0.275	0.609517086792	gnomAD-4.0.0	6.57065E-06	None	None	None	None	N	None	2.41208E-05	0	None	0	0	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	0.2173	likely_benign	0.2001	benign	-1.02	Destabilizing	0.025	N	0.538	neutral	None	None	None	None	N
N/C	0.1216	likely_benign	0.135	benign	-0.081	Destabilizing	None	N	0.478	neutral	None	None	None	None	N
N/D	0.2392	likely_benign	0.2339	benign	-0.912	Destabilizing	0.081	N	0.444	neutral	N	0.467757272	None	None	N
N/E	0.5308	ambiguous	0.517	ambiguous	-0.711	Destabilizing	0.124	N	0.45	neutral	None	None	None	None	N
N/F	0.6442	likely_pathogenic	0.6096	pathogenic	-0.4	Destabilizing	0.667	D	0.658	neutral	None	None	None	None	N
N/G	0.2818	likely_benign	0.2574	benign	-1.437	Destabilizing	0.055	N	0.413	neutral	None	None	None	None	N
N/H	0.16	likely_benign	0.1522	benign	-0.843	Destabilizing	0.602	D	0.56	neutral	N	0.457060276	None	None	N
N/I	0.2368	likely_benign	0.2282	benign	0.097	Stabilizing	0.096	N	0.618	neutral	N	0.449075511	None	None	N
N/K	0.5766	likely_pathogenic	0.5299	ambiguous	-0.227	Destabilizing	0.096	N	0.43	neutral	N	0.435700782	None	None	N
N/L	0.3278	likely_benign	0.3115	benign	0.097	Stabilizing	0.055	N	0.562	neutral	None	None	None	None	N
N/M	0.3343	likely_benign	0.3259	benign	0.35	Stabilizing	0.667	D	0.596	neutral	None	None	None	None	N
N/P	0.9601	likely_pathogenic	0.9577	pathogenic	-0.247	Destabilizing	0.364	N	0.609	neutral	None	None	None	None	N
N/Q	0.4458	ambiguous	0.4225	ambiguous	-0.674	Destabilizing	0.22	N	0.55	neutral	None	None	None	None	N
N/R	0.6159	likely_pathogenic	0.5774	pathogenic	-0.387	Destabilizing	0.22	N	0.527	neutral	None	None	None	None	N
N/S	0.0867	likely_benign	0.0794	benign	-1.093	Destabilizing	None	N	0.203	neutral	N	0.384850674	None	None	N
N/T	0.1207	likely_benign	0.1151	benign	-0.688	Destabilizing	None	N	0.197	neutral	N	0.412133276	None	None	N
N/V	0.226	likely_benign	0.2208	benign	-0.247	Destabilizing	0.055	N	0.559	neutral	None	None	None	None	N
N/W	0.8331	likely_pathogenic	0.8242	pathogenic	-0.178	Destabilizing	0.958	D	0.633	neutral	None	None	None	None	N
N/Y	0.1706	likely_benign	0.1743	benign	0.075	Stabilizing	0.602	D	0.611	neutral	N	0.457406992	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.