TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15748	47467;47468;47469	chr2:178618216;178618215;178618214	chr2:179482943;179482942;179482941
N2AB	14107	42544;42545;42546	chr2:178618216;178618215;178618214	chr2:179482943;179482942;179482941
N2A	13180	39763;39764;39765	chr2:178618216;178618215;178618214	chr2:179482943;179482942;179482941
N2B	6683	20272;20273;20274	chr2:178618216;178618215;178618214	chr2:179482943;179482942;179482941
Novex-1	6808	20647;20648;20649	chr2:178618216;178618215;178618214	chr2:179482943;179482942;179482941
Novex-2	6875	20848;20849;20850	chr2:178618216;178618215;178618214	chr2:179482943;179482942;179482941
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-1
• Domain position: 92
• Structural Position: 125
• Q(SASA): 0.5769
• 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
N/H	rs368988689	-0.234	0.162	N	0.285	0.126	None	gnomAD-2.1.1	1.79E-05	None	None	None	None	N	None	2.06902E-04	0	None	0	0	None	0	None	0	0	0
N/H	rs368988689	-0.234	0.162	N	0.285	0.126	None	gnomAD-3.1.2	8.56E-05	None	None	None	None	N	None	2.89715E-04	0	0	0	0	None	0	0	0	0	4.78927E-04
N/H	rs368988689	-0.234	0.162	N	0.285	0.126	None	gnomAD-4.0.0	1.55027E-05	None	None	None	None	N	None	2.80689E-04	0	None	0	0	None	0	0	8.48064E-07	0	4.80831E-05
N/S	None	None	None	N	0.052	0.103	0.0611884634855	gnomAD-4.0.0	2.05384E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69963E-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	0.0899	likely_benign	0.0777	benign	-0.041	Destabilizing	0.003	N	0.248	neutral	None	None	None	None	N
N/C	0.1539	likely_benign	0.108	benign	0.209	Stabilizing	0.492	N	0.368	neutral	None	None	None	None	N
N/D	0.1052	likely_benign	0.0964	benign	0.198	Stabilizing	None	N	0.065	neutral	N	0.383529297	None	None	N
N/E	0.133	likely_benign	0.1167	benign	0.149	Stabilizing	0.003	N	0.141	neutral	None	None	None	None	N
N/F	0.2286	likely_benign	0.195	benign	-0.627	Destabilizing	0.204	N	0.549	neutral	None	None	None	None	N
N/G	0.1738	likely_benign	0.1317	benign	-0.153	Destabilizing	0.003	N	0.145	neutral	None	None	None	None	N
N/H	0.071	likely_benign	0.0639	benign	-0.189	Destabilizing	0.162	N	0.285	neutral	N	0.491481201	None	None	N
N/I	0.0661	likely_benign	0.077	benign	0.154	Stabilizing	0.026	N	0.576	neutral	N	0.488724841	None	None	N
N/K	0.0811	likely_benign	0.0737	benign	0.153	Stabilizing	None	N	0.071	neutral	N	0.379849813	None	None	N
N/L	0.092	likely_benign	0.0868	benign	0.154	Stabilizing	0.007	N	0.303	neutral	None	None	None	None	N
N/M	0.1304	likely_benign	0.1239	benign	0.127	Stabilizing	0.439	N	0.415	neutral	None	None	None	None	N
N/P	0.608	likely_pathogenic	0.5455	ambiguous	0.113	Stabilizing	0.035	N	0.431	neutral	None	None	None	None	N
N/Q	0.1046	likely_benign	0.0903	benign	-0.152	Destabilizing	0.035	N	0.151	neutral	None	None	None	None	N
N/R	0.1018	likely_benign	0.0846	benign	0.184	Stabilizing	None	N	0.065	neutral	None	None	None	None	N
N/S	0.0615	likely_benign	0.059	benign	0.033	Stabilizing	None	N	0.052	neutral	N	0.466455781	None	None	N
N/T	0.057	likely_benign	0.0538	benign	0.103	Stabilizing	None	N	0.061	neutral	N	0.458813224	None	None	N
N/V	0.0734	likely_benign	0.0781	benign	0.113	Stabilizing	0.007	N	0.391	neutral	None	None	None	None	N
N/W	0.4998	ambiguous	0.3854	ambiguous	-0.771	Destabilizing	0.747	D	0.399	neutral	None	None	None	None	N
N/Y	0.1126	likely_benign	0.0961	benign	-0.43	Destabilizing	0.162	N	0.558	neutral	N	0.499339559	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.