TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32138	96637;96638;96639	chr2:178543561;178543560;178543559	chr2:179408288;179408287;179408286
N2AB	30497	91714;91715;91716	chr2:178543561;178543560;178543559	chr2:179408288;179408287;179408286
N2A	29570	88933;88934;88935	chr2:178543561;178543560;178543559	chr2:179408288;179408287;179408286
N2B	23073	69442;69443;69444	chr2:178543561;178543560;178543559	chr2:179408288;179408287;179408286
Novex-1	23198	69817;69818;69819	chr2:178543561;178543560;178543559	chr2:179408288;179408287;179408286
Novex-2	23265	70018;70019;70020	chr2:178543561;178543560;178543559	chr2:179408288;179408287;179408286
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-122
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.5638
• Predicted PPI site: I

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
N/I	None	None	0.188	N	0.445	0.233	0.245101548738	gnomAD-4.0.0	3.19598E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.71759E-06	0	0
N/K	rs933403975	None	0.062	N	0.325	0.114	0.134241683229	gnomAD-4.0.0	4.11286E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.39714E-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
N/A	0.1664	likely_benign	0.183	benign	-0.466	Destabilizing	0.035	N	0.397	neutral	None	None	None	None	I
N/C	0.1453	likely_benign	0.1622	benign	0.352	Stabilizing	0.824	D	0.401	neutral	None	None	None	None	I
N/D	0.2983	likely_benign	0.3157	benign	-0.094	Destabilizing	0.062	N	0.335	neutral	N	0.430454385	None	None	I
N/E	0.4815	ambiguous	0.502	ambiguous	-0.102	Destabilizing	0.081	N	0.32	neutral	None	None	None	None	I
N/F	0.4317	ambiguous	0.4693	ambiguous	-0.65	Destabilizing	0.555	D	0.438	neutral	None	None	None	None	I
N/G	0.2023	likely_benign	0.221	benign	-0.691	Destabilizing	0.035	N	0.387	neutral	None	None	None	None	I
N/H	0.0918	likely_benign	0.1079	benign	-0.708	Destabilizing	0.484	N	0.408	neutral	N	0.483944941	None	None	I
N/I	0.1466	likely_benign	0.1621	benign	0.055	Stabilizing	0.188	N	0.445	neutral	N	0.407022952	None	None	I
N/K	0.3012	likely_benign	0.33	benign	-0.025	Destabilizing	0.062	N	0.325	neutral	N	0.414679643	None	None	I
N/L	0.1614	likely_benign	0.1777	benign	0.055	Stabilizing	0.081	N	0.399	neutral	None	None	None	None	I
N/M	0.2253	likely_benign	0.2465	benign	0.532	Stabilizing	0.824	D	0.403	neutral	None	None	None	None	I
N/P	0.8019	likely_pathogenic	0.7951	pathogenic	-0.09	Destabilizing	0.38	N	0.413	neutral	None	None	None	None	I
N/Q	0.2645	likely_benign	0.2972	benign	-0.511	Destabilizing	0.38	N	0.401	neutral	None	None	None	None	I
N/R	0.3271	likely_benign	0.3492	ambiguous	0.021	Stabilizing	0.149	N	0.377	neutral	None	None	None	None	I
N/S	0.0643	likely_benign	0.067	benign	-0.299	Destabilizing	None	N	0.059	neutral	N	0.350764238	None	None	I
N/T	0.0783	likely_benign	0.0836	benign	-0.152	Destabilizing	None	N	0.087	neutral	N	0.342045967	None	None	I
N/V	0.1521	likely_benign	0.1644	benign	-0.09	Destabilizing	0.081	N	0.423	neutral	None	None	None	None	I
N/W	0.6879	likely_pathogenic	0.7123	pathogenic	-0.548	Destabilizing	0.935	D	0.583	neutral	None	None	None	None	I
N/Y	0.1421	likely_benign	0.164	benign	-0.318	Destabilizing	0.484	N	0.429	neutral	N	0.50280006	None	None	I

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.