TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29124	87595;87596;87597	chr2:178557984;178557983;178557982	chr2:179422711;179422710;179422709
N2AB	27483	82672;82673;82674	chr2:178557984;178557983;178557982	chr2:179422711;179422710;179422709
N2A	26556	79891;79892;79893	chr2:178557984;178557983;178557982	chr2:179422711;179422710;179422709
N2B	20059	60400;60401;60402	chr2:178557984;178557983;178557982	chr2:179422711;179422710;179422709
Novex-1	20184	60775;60776;60777	chr2:178557984;178557983;178557982	chr2:179422711;179422710;179422709
Novex-2	20251	60976;60977;60978	chr2:178557984;178557983;178557982	chr2:179422711;179422710;179422709
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-145
• Domain position: 80
• Structural Position: 164
• Q(SASA): 0.1915
• 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
G/D	None	None	1.0	D	0.853	0.768	0.53586618445	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
G/A	0.4581	ambiguous	0.516	ambiguous	-0.096	Destabilizing	1.0	D	0.734	prob.delet.	D	0.571351422	None	None	N
G/C	0.6324	likely_pathogenic	0.6956	pathogenic	-0.76	Destabilizing	1.0	D	0.803	deleterious	D	0.572562247	None	None	N
G/D	0.833	likely_pathogenic	0.8903	pathogenic	-0.38	Destabilizing	1.0	D	0.853	deleterious	D	0.586967174	None	None	N
G/E	0.8633	likely_pathogenic	0.9153	pathogenic	-0.539	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
G/F	0.9465	likely_pathogenic	0.9602	pathogenic	-0.945	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
G/H	0.9004	likely_pathogenic	0.9289	pathogenic	-0.332	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
G/I	0.9093	likely_pathogenic	0.9376	pathogenic	-0.375	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
G/K	0.8937	likely_pathogenic	0.9308	pathogenic	-0.363	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
G/L	0.9115	likely_pathogenic	0.9394	pathogenic	-0.375	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
G/M	0.9192	likely_pathogenic	0.9428	pathogenic	-0.389	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
G/N	0.7988	likely_pathogenic	0.8573	pathogenic	-0.13	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
G/P	0.9972	likely_pathogenic	0.9972	pathogenic	-0.258	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
G/Q	0.8186	likely_pathogenic	0.8708	pathogenic	-0.386	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
G/R	0.7867	likely_pathogenic	0.8405	pathogenic	-0.046	Destabilizing	1.0	D	0.859	deleterious	D	0.587572587	None	None	N
G/S	0.3372	likely_benign	0.3754	ambiguous	-0.24	Destabilizing	1.0	D	0.792	deleterious	D	0.58676537	None	None	N
G/T	0.7283	likely_pathogenic	0.783	pathogenic	-0.336	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
G/V	0.8329	likely_pathogenic	0.8798	pathogenic	-0.258	Destabilizing	1.0	D	0.837	deleterious	D	0.588178	None	None	N
G/W	0.9368	likely_pathogenic	0.9515	pathogenic	-1.074	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
G/Y	0.9201	likely_pathogenic	0.9414	pathogenic	-0.726	Destabilizing	1.0	D	0.832	deleterious	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.