TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6649	20170;20171;20172	chr2:178727633;178727632;178727631	chr2:179592360;179592359;179592358
N2AB	6332	19219;19220;19221	chr2:178727633;178727632;178727631	chr2:179592360;179592359;179592358
N2A	5405	16438;16439;16440	chr2:178727633;178727632;178727631	chr2:179592360;179592359;179592358
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: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-50
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.2107
• 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
T/I	rs767035458	-0.013	0.351	D	0.46	0.261	0.537402380065	gnomAD-2.1.1	4.2E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.17E-06	0
T/I	rs767035458	-0.013	0.351	D	0.46	0.261	0.537402380065	gnomAD-4.0.0	1.62667E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.9108E-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
T/A	0.0883	likely_benign	0.088	benign	-0.975	Destabilizing	0.001	N	0.114	neutral	N	0.485861048	None	None	N
T/C	0.451	ambiguous	0.4663	ambiguous	-0.713	Destabilizing	0.836	D	0.479	neutral	None	None	None	None	N
T/D	0.3572	ambiguous	0.3602	ambiguous	-0.654	Destabilizing	0.418	N	0.471	neutral	None	None	None	None	N
T/E	0.2684	likely_benign	0.2637	benign	-0.651	Destabilizing	0.418	N	0.459	neutral	None	None	None	None	N
T/F	0.2465	likely_benign	0.2526	benign	-1.105	Destabilizing	0.002	N	0.384	neutral	None	None	None	None	N
T/G	0.259	likely_benign	0.2664	benign	-1.225	Destabilizing	0.129	N	0.546	neutral	None	None	None	None	N
T/H	0.2531	likely_benign	0.288	benign	-1.532	Destabilizing	0.94	D	0.531	neutral	None	None	None	None	N
T/I	0.1937	likely_benign	0.1962	benign	-0.396	Destabilizing	0.351	N	0.46	neutral	D	0.525173567	None	None	N
T/K	0.2148	likely_benign	0.2244	benign	-0.834	Destabilizing	0.418	N	0.457	neutral	None	None	None	None	N
T/L	0.1317	likely_benign	0.1293	benign	-0.396	Destabilizing	0.129	N	0.459	neutral	None	None	None	None	N
T/M	0.1007	likely_benign	0.0994	benign	-0.011	Destabilizing	0.94	D	0.481	neutral	None	None	None	None	N
T/N	0.1307	likely_benign	0.1313	benign	-0.832	Destabilizing	0.351	N	0.397	neutral	N	0.486875006	None	None	N
T/P	0.6268	likely_pathogenic	0.6166	pathogenic	-0.558	Destabilizing	0.523	D	0.489	neutral	D	0.52393289	None	None	N
T/Q	0.2051	likely_benign	0.2191	benign	-1.072	Destabilizing	0.836	D	0.469	neutral	None	None	None	None	N
T/R	0.161	likely_benign	0.1678	benign	-0.558	Destabilizing	0.418	N	0.484	neutral	None	None	None	None	N
T/S	0.094	likely_benign	0.0974	benign	-1.098	Destabilizing	0.001	N	0.123	neutral	N	0.415253725	None	None	N
T/V	0.1579	likely_benign	0.1636	benign	-0.558	Destabilizing	0.129	N	0.37	neutral	None	None	None	None	N
T/W	0.5679	likely_pathogenic	0.6074	pathogenic	-1.004	Destabilizing	0.983	D	0.511	neutral	None	None	None	None	N
T/Y	0.2944	likely_benign	0.3159	benign	-0.766	Destabilizing	0.557	D	0.535	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.