TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28019	84280;84281;84282	chr2:178562077;178562076;178562075	chr2:179426804;179426803;179426802
N2AB	26378	79357;79358;79359	chr2:178562077;178562076;178562075	chr2:179426804;179426803;179426802
N2A	25451	76576;76577;76578	chr2:178562077;178562076;178562075	chr2:179426804;179426803;179426802
N2B	18954	57085;57086;57087	chr2:178562077;178562076;178562075	chr2:179426804;179426803;179426802
Novex-1	19079	57460;57461;57462	chr2:178562077;178562076;178562075	chr2:179426804;179426803;179426802
Novex-2	19146	57661;57662;57663	chr2:178562077;178562076;178562075	chr2:179426804;179426803;179426802
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-142
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.2518
• 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/L	rs769665204	-0.246	None	N	0.259	0.119	0.525049811399	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.98E-06	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	0.08	likely_benign	0.0847	benign	-1.058	Destabilizing	0.005	N	0.327	neutral	D	0.522093189	None	None	N
S/C	0.0847	likely_benign	0.0858	benign	-1.091	Destabilizing	0.356	N	0.527	neutral	None	None	None	None	N
S/D	0.5222	ambiguous	0.5723	pathogenic	-1.337	Destabilizing	0.072	N	0.335	neutral	None	None	None	None	N
S/E	0.4584	ambiguous	0.5001	ambiguous	-1.222	Destabilizing	0.031	N	0.314	neutral	None	None	None	None	N
S/F	0.1641	likely_benign	0.1812	benign	-1.282	Destabilizing	None	N	0.339	neutral	None	None	None	None	N
S/G	0.1254	likely_benign	0.1373	benign	-1.363	Destabilizing	0.031	N	0.335	neutral	None	None	None	None	N
S/H	0.2553	likely_benign	0.2572	benign	-1.779	Destabilizing	0.628	D	0.531	neutral	None	None	None	None	N
S/I	0.1327	likely_benign	0.1329	benign	-0.315	Destabilizing	0.038	N	0.433	neutral	None	None	None	None	N
S/K	0.5577	ambiguous	0.5905	pathogenic	-0.552	Destabilizing	None	N	0.095	neutral	None	None	None	None	N
S/L	0.1031	likely_benign	0.1099	benign	-0.315	Destabilizing	None	N	0.259	neutral	N	0.479073131	None	None	N
S/M	0.1536	likely_benign	0.1582	benign	-0.185	Destabilizing	0.214	N	0.527	neutral	None	None	None	None	N
S/N	0.153	likely_benign	0.1572	benign	-1.055	Destabilizing	0.072	N	0.332	neutral	None	None	None	None	N
S/P	0.9141	likely_pathogenic	0.939	pathogenic	-0.531	Destabilizing	0.106	N	0.523	neutral	N	0.499383401	None	None	N
S/Q	0.3768	ambiguous	0.3931	ambiguous	-1.063	Destabilizing	0.072	N	0.429	neutral	None	None	None	None	N
S/R	0.4629	ambiguous	0.5061	ambiguous	-0.655	Destabilizing	0.038	N	0.439	neutral	None	None	None	None	N
S/T	0.0643	likely_benign	0.0626	benign	-0.871	Destabilizing	None	N	0.083	neutral	N	0.468639919	None	None	N
S/V	0.126	likely_benign	0.1268	benign	-0.531	Destabilizing	0.016	N	0.39	neutral	None	None	None	None	N
S/W	0.326	likely_benign	0.3657	ambiguous	-1.346	Destabilizing	0.864	D	0.544	neutral	None	None	None	None	N
S/Y	0.1553	likely_benign	0.1715	benign	-0.971	Destabilizing	0.038	N	0.541	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.