TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18263	55012;55013;55014	chr2:178603900;178603899;178603898	chr2:179468627;179468626;179468625
N2AB	16622	50089;50090;50091	chr2:178603900;178603899;178603898	chr2:179468627;179468626;179468625
N2A	15695	47308;47309;47310	chr2:178603900;178603899;178603898	chr2:179468627;179468626;179468625
N2B	9198	27817;27818;27819	chr2:178603900;178603899;178603898	chr2:179468627;179468626;179468625
Novex-1	9323	28192;28193;28194	chr2:178603900;178603899;178603898	chr2:179468627;179468626;179468625
Novex-2	9390	28393;28394;28395	chr2:178603900;178603899;178603898	chr2:179468627;179468626;179468625
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-20
• Domain position: 98
• Structural Position: 126
• Q(SASA): 0.3597
• 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
P/A	None	None	0.104	N	0.393	0.256	0.203808441222	gnomAD-4.0.0	1.60278E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.88509E-06	0	0
P/L	None	None	0.002	N	0.471	0.142	0.358134431457	gnomAD-4.0.0	6.86437E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.0221E-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
P/A	0.0705	likely_benign	0.0605	benign	-0.924	Destabilizing	0.104	N	0.393	neutral	N	0.519590736	None	None	N
P/C	0.3727	ambiguous	0.315	benign	-0.63	Destabilizing	0.005	N	0.479	neutral	None	None	None	None	N
P/D	0.5224	ambiguous	0.4207	ambiguous	-0.943	Destabilizing	0.428	N	0.464	neutral	None	None	None	None	N
P/E	0.3388	likely_benign	0.2463	benign	-1.051	Destabilizing	0.428	N	0.45	neutral	None	None	None	None	N
P/F	0.4226	ambiguous	0.2806	benign	-1.029	Destabilizing	0.568	D	0.582	neutral	None	None	None	None	N
P/G	0.2942	likely_benign	0.2188	benign	-1.101	Destabilizing	0.428	N	0.504	neutral	None	None	None	None	N
P/H	0.2922	likely_benign	0.2114	benign	-0.62	Destabilizing	0.984	D	0.552	neutral	None	None	None	None	N
P/I	0.243	likely_benign	0.1716	benign	-0.586	Destabilizing	0.272	N	0.577	neutral	None	None	None	None	N
P/K	0.4198	ambiguous	0.2952	benign	-0.809	Destabilizing	0.428	N	0.47	neutral	None	None	None	None	N
P/L	0.1218	likely_benign	0.0831	benign	-0.586	Destabilizing	0.002	N	0.471	neutral	N	0.460143248	None	None	N
P/M	0.2404	likely_benign	0.1782	benign	-0.39	Destabilizing	0.724	D	0.555	neutral	None	None	None	None	N
P/N	0.4181	ambiguous	0.3236	benign	-0.47	Destabilizing	0.724	D	0.555	neutral	None	None	None	None	N
P/Q	0.2725	likely_benign	0.1928	benign	-0.787	Destabilizing	0.8	D	0.516	neutral	N	0.499633895	None	None	N
P/R	0.3095	likely_benign	0.199	benign	-0.149	Destabilizing	0.8	D	0.558	neutral	N	0.495025539	None	None	N
P/S	0.1303	likely_benign	0.1077	benign	-0.818	Destabilizing	0.009	N	0.267	neutral	N	0.50760566	None	None	N
P/T	0.0975	likely_benign	0.087	benign	-0.836	Destabilizing	0.22	N	0.521	neutral	N	0.480933756	None	None	N
P/V	0.1566	likely_benign	0.1208	benign	-0.664	Destabilizing	0.272	N	0.503	neutral	None	None	None	None	N
P/W	0.6216	likely_pathogenic	0.4372	ambiguous	-1.094	Destabilizing	0.984	D	0.639	neutral	None	None	None	None	N
P/Y	0.4514	ambiguous	0.3172	benign	-0.83	Destabilizing	0.842	D	0.595	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.