TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6443	19552;19553;19554	chr2:178728599;178728598;178728597	chr2:179593326;179593325;179593324
N2AB	6126	18601;18602;18603	chr2:178728599;178728598;178728597	chr2:179593326;179593325;179593324
N2A	5199	15820;15821;15822	chr2:178728599;178728598;178728597	chr2:179593326;179593325;179593324
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: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-48
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.5659
• 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
R/S	rs1217984218	None	0.92	N	0.559	0.463	0.38342384377	gnomAD-4.0.0	6.84456E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99633E-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
R/A	0.5752	likely_pathogenic	0.5501	ambiguous	-1.463	Destabilizing	0.863	D	0.549	neutral	None	None	None	None	N
R/C	0.2457	likely_benign	0.2163	benign	-1.484	Destabilizing	0.999	D	0.597	neutral	None	None	None	None	N
R/D	0.8226	likely_pathogenic	0.7894	pathogenic	-0.372	Destabilizing	0.969	D	0.572	neutral	None	None	None	None	N
R/E	0.4918	ambiguous	0.4448	ambiguous	-0.231	Destabilizing	0.863	D	0.621	neutral	None	None	None	None	N
R/F	0.6514	likely_pathogenic	0.619	pathogenic	-1.246	Destabilizing	0.997	D	0.6	neutral	None	None	None	None	N
R/G	0.4544	ambiguous	0.4242	ambiguous	-1.775	Destabilizing	0.959	D	0.553	neutral	N	0.517668804	None	None	N
R/H	0.0999	likely_benign	0.0966	benign	-1.787	Destabilizing	0.997	D	0.616	neutral	None	None	None	None	N
R/I	0.3152	likely_benign	0.293	benign	-0.602	Destabilizing	0.996	D	0.603	neutral	N	0.478128981	None	None	N
R/K	0.119	likely_benign	0.1177	benign	-1.303	Destabilizing	0.021	N	0.369	neutral	N	0.387875123	None	None	N
R/L	0.3347	likely_benign	0.3121	benign	-0.602	Destabilizing	0.969	D	0.553	neutral	None	None	None	None	N
R/M	0.3615	ambiguous	0.3398	benign	-0.876	Destabilizing	0.997	D	0.589	neutral	None	None	None	None	N
R/N	0.6927	likely_pathogenic	0.6648	pathogenic	-0.778	Destabilizing	0.969	D	0.578	neutral	None	None	None	None	N
R/P	0.9658	likely_pathogenic	0.9584	pathogenic	-0.872	Destabilizing	0.997	D	0.581	neutral	None	None	None	None	N
R/Q	0.1063	likely_benign	0.0995	benign	-0.983	Destabilizing	0.939	D	0.61	neutral	None	None	None	None	N
R/S	0.5614	ambiguous	0.5325	ambiguous	-1.751	Destabilizing	0.92	D	0.559	neutral	N	0.506027658	None	None	N
R/T	0.2878	likely_benign	0.2685	benign	-1.419	Destabilizing	0.959	D	0.532	neutral	N	0.456846845	None	None	N
R/V	0.4275	ambiguous	0.4108	ambiguous	-0.872	Destabilizing	0.991	D	0.585	neutral	None	None	None	None	N
R/W	0.2175	likely_benign	0.1997	benign	-0.749	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
R/Y	0.4859	ambiguous	0.4408	ambiguous	-0.5	Destabilizing	0.997	D	0.59	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.