TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29335	88228;88229;88230	chr2:178557259;178557258;178557257	chr2:179421986;179421985;179421984
N2AB	27694	83305;83306;83307	chr2:178557259;178557258;178557257	chr2:179421986;179421985;179421984
N2A	26767	80524;80525;80526	chr2:178557259;178557258;178557257	chr2:179421986;179421985;179421984
N2B	20270	61033;61034;61035	chr2:178557259;178557258;178557257	chr2:179421986;179421985;179421984
Novex-1	20395	61408;61409;61410	chr2:178557259;178557258;178557257	chr2:179421986;179421985;179421984
Novex-2	20462	61609;61610;61611	chr2:178557259;178557258;178557257	chr2:179421986;179421985;179421984
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-102
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.8455
• Predicted PPI site: I

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
A/P	None	None	0.999	N	0.713	0.358	0.344483371355	gnomAD-4.0.0	2.05262E-06	None	None	None	None	I	None	0	0	None	0	2.52411E-05	None	0	0	1.79885E-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
A/C	0.5618	ambiguous	0.5557	ambiguous	-0.809	Destabilizing	1.0	D	0.673	prob.neutral	None	None	None	None	I
A/D	0.5562	ambiguous	0.484	ambiguous	0.143	Stabilizing	0.997	D	0.824	deleterious	N	0.480797487	None	None	I
A/E	0.5003	ambiguous	0.4436	ambiguous	0.008	Stabilizing	0.998	D	0.669	prob.neutral	None	None	None	None	I
A/F	0.563	ambiguous	0.5204	ambiguous	-0.777	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
A/G	0.225	likely_benign	0.2198	benign	-0.281	Destabilizing	0.991	D	0.566	neutral	N	0.480624129	None	None	I
A/H	0.6353	likely_pathogenic	0.5953	pathogenic	-0.276	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	I
A/I	0.3753	ambiguous	0.3515	ambiguous	-0.294	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	I
A/K	0.7031	likely_pathogenic	0.6423	pathogenic	-0.35	Destabilizing	0.998	D	0.697	prob.delet.	None	None	None	None	I
A/L	0.2817	likely_benign	0.2665	benign	-0.294	Destabilizing	0.997	D	0.77	deleterious	None	None	None	None	I
A/M	0.3474	ambiguous	0.3417	ambiguous	-0.442	Destabilizing	1.0	D	0.689	prob.delet.	None	None	None	None	I
A/N	0.365	ambiguous	0.3335	benign	-0.107	Destabilizing	0.998	D	0.815	deleterious	None	None	None	None	I
A/P	0.1964	likely_benign	0.1987	benign	-0.242	Destabilizing	0.999	D	0.713	prob.delet.	N	0.295206451	None	None	I
A/Q	0.4763	ambiguous	0.4423	ambiguous	-0.308	Destabilizing	0.999	D	0.699	prob.delet.	None	None	None	None	I
A/R	0.618	likely_pathogenic	0.5543	ambiguous	-0.028	Destabilizing	0.999	D	0.699	prob.delet.	None	None	None	None	I
A/S	0.1106	likely_benign	0.1114	benign	-0.403	Destabilizing	0.911	D	0.27	neutral	N	0.432062178	None	None	I
A/T	0.1242	likely_benign	0.1274	benign	-0.442	Destabilizing	0.983	D	0.699	prob.delet.	N	0.479930696	None	None	I
A/V	0.1932	likely_benign	0.184	benign	-0.242	Destabilizing	0.996	D	0.73	deleterious	N	0.424458628	None	None	I
A/W	0.9054	likely_pathogenic	0.8849	pathogenic	-0.895	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
A/Y	0.6759	likely_pathogenic	0.6378	pathogenic	-0.547	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I

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.