TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17142	51649;51650;51651	chr2:178610102;178610101;178610100	chr2:179474829;179474828;179474827
N2AB	15501	46726;46727;46728	chr2:178610102;178610101;178610100	chr2:179474829;179474828;179474827
N2A	14574	43945;43946;43947	chr2:178610102;178610101;178610100	chr2:179474829;179474828;179474827
N2B	8077	24454;24455;24456	chr2:178610102;178610101;178610100	chr2:179474829;179474828;179474827
Novex-1	8202	24829;24830;24831	chr2:178610102;178610101;178610100	chr2:179474829;179474828;179474827
Novex-2	8269	25030;25031;25032	chr2:178610102;178610101;178610100	chr2:179474829;179474828;179474827
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Fn3-12
• Domain position: 96
• Structural Position: 131
• Q(SASA): 0.446
• 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
Q/K	None	None	0.278	N	0.297	0.101	0.162503812791	gnomAD-4.0.0	6.84643E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99836E-07	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
Q/A	0.2278	likely_benign	0.2293	benign	-0.446	Destabilizing	0.505	D	0.235	neutral	None	None	None	None	N
Q/C	0.7596	likely_pathogenic	0.7285	pathogenic	0.205	Stabilizing	0.995	D	0.569	neutral	None	None	None	None	N
Q/D	0.6918	likely_pathogenic	0.628	pathogenic	-0.413	Destabilizing	0.338	N	0.244	neutral	None	None	None	None	N
Q/E	0.0974	likely_benign	0.0899	benign	-0.381	Destabilizing	0.001	N	0.103	neutral	N	0.380793569	None	None	N
Q/F	0.8543	likely_pathogenic	0.8183	pathogenic	-0.372	Destabilizing	0.982	D	0.512	neutral	None	None	None	None	N
Q/G	0.4071	ambiguous	0.3664	ambiguous	-0.74	Destabilizing	0.712	D	0.371	neutral	None	None	None	None	N
Q/H	0.4371	ambiguous	0.395	ambiguous	-0.798	Destabilizing	0.93	D	0.291	neutral	N	0.497140737	None	None	N
Q/I	0.4738	ambiguous	0.4521	ambiguous	0.271	Stabilizing	0.946	D	0.611	neutral	None	None	None	None	N
Q/K	0.2344	likely_benign	0.1624	benign	-0.246	Destabilizing	0.278	N	0.297	neutral	N	0.359786366	None	None	N
Q/L	0.2256	likely_benign	0.2005	benign	0.271	Stabilizing	0.651	D	0.337	neutral	N	0.43684164	None	None	N
Q/M	0.3777	ambiguous	0.39	ambiguous	0.771	Stabilizing	0.982	D	0.282	neutral	None	None	None	None	N
Q/N	0.4571	ambiguous	0.444	ambiguous	-0.621	Destabilizing	0.712	D	0.239	neutral	None	None	None	None	N
Q/P	0.899	likely_pathogenic	0.8247	pathogenic	0.063	Stabilizing	0.791	D	0.409	neutral	N	0.443303466	None	None	N
Q/R	0.2541	likely_benign	0.1772	benign	-0.169	Destabilizing	0.651	D	0.385	neutral	N	0.36804049	None	None	N
Q/S	0.2538	likely_benign	0.2712	benign	-0.644	Destabilizing	0.505	D	0.221	neutral	None	None	None	None	N
Q/T	0.2096	likely_benign	0.2204	benign	-0.437	Destabilizing	0.712	D	0.296	neutral	None	None	None	None	N
Q/V	0.2623	likely_benign	0.2638	benign	0.063	Stabilizing	0.834	D	0.394	neutral	None	None	None	None	N
Q/W	0.8803	likely_pathogenic	0.8095	pathogenic	-0.297	Destabilizing	0.995	D	0.555	neutral	None	None	None	None	N
Q/Y	0.746	likely_pathogenic	0.6836	pathogenic	-0.072	Destabilizing	0.982	D	0.46	neutral	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.