TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3109	9550;9551;9552	chr2:178767905;178767904;178767903	chr2:179632632;179632631;179632630
N2AB	3109	9550;9551;9552	chr2:178767905;178767904;178767903	chr2:179632632;179632631;179632630
N2A	3109	9550;9551;9552	chr2:178767905;178767904;178767903	chr2:179632632;179632631;179632630
N2B	3063	9412;9413;9414	chr2:178767905;178767904;178767903	chr2:179632632;179632631;179632630
Novex-1	3063	9412;9413;9414	chr2:178767905;178767904;178767903	chr2:179632632;179632631;179632630
Novex-2	3063	9412;9413;9414	chr2:178767905;178767904;178767903	chr2:179632632;179632631;179632630
Novex-3	3109	9550;9551;9552	chr2:178767905;178767904;178767903	chr2:179632632;179632631;179632630

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-21
• Domain position: 52
• Structural Position: 131
• Q(SASA): 0.616
• 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
K/R	rs753036867	-0.007	0.02	N	0.245	0.107	None	gnomAD-2.1.1	1.77E-05	None	None	None	None	N	None	2.0024E-04	0	None	0	0	None	0	None	0	0	0
K/R	rs753036867	-0.007	0.02	N	0.245	0.107	None	gnomAD-3.1.2	6.57E-05	None	None	None	None	N	None	2.41336E-04	0	0	0	0	None	0	0	0	0	0
K/R	rs753036867	-0.007	0.02	N	0.245	0.107	None	gnomAD-4.0.0	1.11527E-05	None	None	None	None	N	None	2.40276E-04	0	None	0	0	None	0	0	0	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
K/A	0.7223	likely_pathogenic	0.7043	pathogenic	-0.382	Destabilizing	0.953	D	0.482	neutral	None	None	None	None	N
K/C	0.9231	likely_pathogenic	0.9136	pathogenic	-0.395	Destabilizing	0.999	D	0.611	neutral	None	None	None	None	N
K/D	0.8165	likely_pathogenic	0.7827	pathogenic	-0.043	Destabilizing	0.993	D	0.459	neutral	None	None	None	None	N
K/E	0.6098	likely_pathogenic	0.5776	pathogenic	0.051	Stabilizing	0.939	D	0.457	neutral	N	0.475396243	None	None	N
K/F	0.9603	likely_pathogenic	0.9568	pathogenic	-0.177	Destabilizing	0.999	D	0.545	neutral	None	None	None	None	N
K/G	0.6557	likely_pathogenic	0.5963	pathogenic	-0.7	Destabilizing	0.993	D	0.412	neutral	None	None	None	None	N
K/H	0.5732	likely_pathogenic	0.574	pathogenic	-0.96	Destabilizing	0.998	D	0.462	neutral	None	None	None	None	N
K/I	0.8235	likely_pathogenic	0.8287	pathogenic	0.422	Stabilizing	0.991	D	0.559	neutral	N	0.509420387	None	None	N
K/L	0.7457	likely_pathogenic	0.7459	pathogenic	0.422	Stabilizing	0.986	D	0.412	neutral	None	None	None	None	N
K/M	0.6033	likely_pathogenic	0.6126	pathogenic	0.08	Stabilizing	0.999	D	0.47	neutral	None	None	None	None	N
K/N	0.6008	likely_pathogenic	0.5683	pathogenic	-0.241	Destabilizing	0.982	D	0.451	neutral	N	0.476916222	None	None	N
K/P	0.8652	likely_pathogenic	0.8433	pathogenic	0.184	Stabilizing	0.998	D	0.451	neutral	None	None	None	None	N
K/Q	0.342	ambiguous	0.3306	benign	-0.255	Destabilizing	0.982	D	0.46	neutral	N	0.49779072	None	None	N
K/R	0.1054	likely_benign	0.1014	benign	-0.425	Destabilizing	0.02	N	0.245	neutral	N	0.453690294	None	None	N
K/S	0.7563	likely_pathogenic	0.7293	pathogenic	-0.766	Destabilizing	0.953	D	0.422	neutral	None	None	None	None	N
K/T	0.5548	ambiguous	0.5542	ambiguous	-0.48	Destabilizing	0.991	D	0.412	neutral	N	0.502986472	None	None	N
K/V	0.8027	likely_pathogenic	0.7989	pathogenic	0.184	Stabilizing	0.993	D	0.495	neutral	None	None	None	None	N
K/W	0.9335	likely_pathogenic	0.9288	pathogenic	-0.15	Destabilizing	0.999	D	0.639	neutral	None	None	None	None	N
K/Y	0.8644	likely_pathogenic	0.8509	pathogenic	0.137	Stabilizing	0.998	D	0.499	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.