TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6471	19636;19637;19638	chr2:178728515;178728514;178728513	chr2:179593242;179593241;179593240
N2AB	6154	18685;18686;18687	chr2:178728515;178728514;178728513	chr2:179593242;179593241;179593240
N2A	5227	15904;15905;15906	chr2:178728515;178728514;178728513	chr2:179593242;179593241;179593240
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: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-48
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.3553
• 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
Y/C	None	None	0.873	N	0.519	0.282	0.637405007395	gnomAD-4.0.0	2.05747E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.70393E-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
Y/A	0.234	likely_benign	0.2348	benign	-1.256	Destabilizing	0.036	N	0.291	neutral	None	None	None	None	N
Y/C	0.1124	likely_benign	0.1145	benign	-0.112	Destabilizing	0.873	D	0.519	neutral	N	0.463620889	None	None	N
Y/D	0.1348	likely_benign	0.1187	benign	0.685	Stabilizing	0.391	N	0.511	neutral	N	0.429622958	None	None	N
Y/E	0.3252	likely_benign	0.3064	benign	0.695	Stabilizing	0.148	N	0.385	neutral	None	None	None	None	N
Y/F	0.0726	likely_benign	0.0814	benign	-0.617	Destabilizing	None	N	0.115	neutral	N	0.42404378	None	None	N
Y/G	0.3177	likely_benign	0.309	benign	-1.493	Destabilizing	0.26	N	0.418	neutral	None	None	None	None	N
Y/H	0.1041	likely_benign	0.1071	benign	-0.189	Destabilizing	0.873	D	0.457	neutral	N	0.444515053	None	None	N
Y/I	0.2013	likely_benign	0.1997	benign	-0.617	Destabilizing	0.001	N	0.145	neutral	None	None	None	None	N
Y/K	0.3417	ambiguous	0.31	benign	-0.106	Destabilizing	0.001	N	0.217	neutral	None	None	None	None	N
Y/L	0.2497	likely_benign	0.2613	benign	-0.617	Destabilizing	0.016	N	0.231	neutral	None	None	None	None	N
Y/M	0.3586	ambiguous	0.3804	ambiguous	-0.315	Destabilizing	0.596	D	0.52	neutral	None	None	None	None	N
Y/N	0.0937	likely_benign	0.0863	benign	-0.234	Destabilizing	0.391	N	0.491	neutral	N	0.427852089	None	None	N
Y/P	0.6124	likely_pathogenic	0.5647	pathogenic	-0.813	Destabilizing	0.722	D	0.552	neutral	None	None	None	None	N
Y/Q	0.2491	likely_benign	0.2463	benign	-0.22	Destabilizing	0.296	N	0.485	neutral	None	None	None	None	N
Y/R	0.2358	likely_benign	0.2191	benign	0.255	Stabilizing	0.001	N	0.22	neutral	None	None	None	None	N
Y/S	0.0883	likely_benign	0.0843	benign	-0.785	Destabilizing	0.061	N	0.347	neutral	N	0.339827673	None	None	N
Y/T	0.167	likely_benign	0.1656	benign	-0.684	Destabilizing	0.001	N	0.212	neutral	None	None	None	None	N
Y/V	0.1505	likely_benign	0.1531	benign	-0.813	Destabilizing	0.001	N	0.153	neutral	None	None	None	None	N
Y/W	0.3039	likely_benign	0.331	benign	-0.533	Destabilizing	0.901	D	0.486	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.