TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6496	19711;19712;19713	chr2:178728338;178728337;178728336	chr2:179593065;179593064;179593063
N2AB	6179	18760;18761;18762	chr2:178728338;178728337;178728336	chr2:179593065;179593064;179593063
N2A	5252	15979;15980;15981	chr2:178728338;178728337;178728336	chr2:179593065;179593064;179593063
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-49
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.1988
• 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
S/F	rs376604816	-1.158	0.949	N	0.467	0.509	None	gnomAD-2.1.1	1.23E-05	None	None	None	None	N	None	0	0	None	0	5.64E-05	None	0	None	0	1.81E-05	0
S/F	rs376604816	-1.158	0.949	N	0.467	0.509	None	gnomAD-4.0.0	7.53771E-06	None	None	None	None	N	None	0	0	None	0	5.0551E-05	None	0	0	8.10037E-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
S/A	0.1024	likely_benign	0.0995	benign	-0.632	Destabilizing	0.008	N	0.219	neutral	N	0.497113734	None	None	N
S/C	0.168	likely_benign	0.1639	benign	-0.402	Destabilizing	0.986	D	0.402	neutral	N	0.493852862	None	None	N
S/D	0.3188	likely_benign	0.3393	benign	0.424	Stabilizing	0.875	D	0.393	neutral	None	None	None	None	N
S/E	0.471	ambiguous	0.4863	ambiguous	0.38	Stabilizing	0.775	D	0.389	neutral	None	None	None	None	N
S/F	0.206	likely_benign	0.2148	benign	-1.05	Destabilizing	0.949	D	0.467	neutral	N	0.511957117	None	None	N
S/G	0.1023	likely_benign	0.1076	benign	-0.812	Destabilizing	0.633	D	0.422	neutral	None	None	None	None	N
S/H	0.3593	ambiguous	0.383	ambiguous	-1.292	Destabilizing	0.996	D	0.373	neutral	None	None	None	None	N
S/I	0.2584	likely_benign	0.2504	benign	-0.276	Destabilizing	0.923	D	0.459	neutral	None	None	None	None	N
S/K	0.651	likely_pathogenic	0.6885	pathogenic	-0.395	Destabilizing	0.044	N	0.293	neutral	None	None	None	None	N
S/L	0.1335	likely_benign	0.1357	benign	-0.276	Destabilizing	0.633	D	0.443	neutral	None	None	None	None	N
S/M	0.2533	likely_benign	0.252	benign	-0.012	Destabilizing	0.996	D	0.375	neutral	None	None	None	None	N
S/N	0.1485	likely_benign	0.1522	benign	-0.23	Destabilizing	0.875	D	0.442	neutral	None	None	None	None	N
S/P	0.6716	likely_pathogenic	0.6778	pathogenic	-0.363	Destabilizing	0.949	D	0.358	neutral	N	0.499929248	None	None	N
S/Q	0.5018	ambiguous	0.5288	ambiguous	-0.417	Destabilizing	0.923	D	0.385	neutral	None	None	None	None	N
S/R	0.5579	ambiguous	0.6031	pathogenic	-0.303	Destabilizing	0.858	D	0.336	neutral	None	None	None	None	N
S/T	0.0968	likely_benign	0.0966	benign	-0.372	Destabilizing	0.722	D	0.427	neutral	N	0.459984528	None	None	N
S/V	0.2486	likely_benign	0.2423	benign	-0.363	Destabilizing	0.633	D	0.44	neutral	None	None	None	None	N
S/W	0.373	ambiguous	0.3863	ambiguous	-0.987	Destabilizing	0.996	D	0.603	neutral	None	None	None	None	N
S/Y	0.1781	likely_benign	0.1851	benign	-0.717	Destabilizing	0.983	D	0.457	neutral	N	0.475495117	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.