TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33090	99493;99494;99495	chr2:178538561;178538560;178538559	chr2:179403288;179403287;179403286
N2AB	31449	94570;94571;94572	chr2:178538561;178538560;178538559	chr2:179403288;179403287;179403286
N2A	30522	91789;91790;91791	chr2:178538561;178538560;178538559	chr2:179403288;179403287;179403286
N2B	24025	72298;72299;72300	chr2:178538561;178538560;178538559	chr2:179403288;179403287;179403286
Novex-1	24150	72673;72674;72675	chr2:178538561;178538560;178538559	chr2:179403288;179403287;179403286
Novex-2	24217	72874;72875;72876	chr2:178538561;178538560;178538559	chr2:179403288;179403287;179403286
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: Fn3-129
• Domain position: 93
• Structural Position: 126
• Q(SASA): 0.2505
• 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/C	None	None	0.947	N	0.45	0.266	0.453679287548	gnomAD-4.0.0	6.84784E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9992E-07	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	0.0638	likely_benign	0.06	benign	-0.476	Destabilizing	None	N	0.146	neutral	N	0.410322334	None	None	N
S/C	0.1074	likely_benign	0.1103	benign	-0.358	Destabilizing	0.947	D	0.45	neutral	N	0.432545833	None	None	N
S/D	0.5172	ambiguous	0.5503	ambiguous	0.096	Stabilizing	0.524	D	0.397	neutral	None	None	None	None	N
S/E	0.5943	likely_pathogenic	0.6305	pathogenic	0.017	Stabilizing	0.524	D	0.399	neutral	None	None	None	None	N
S/F	0.2158	likely_benign	0.2559	benign	-0.927	Destabilizing	0.855	D	0.511	neutral	N	0.462252665	None	None	N
S/G	0.0691	likely_benign	0.0748	benign	-0.623	Destabilizing	None	N	0.155	neutral	None	None	None	None	N
S/H	0.378	ambiguous	0.4268	ambiguous	-1.088	Destabilizing	0.96	D	0.453	neutral	None	None	None	None	N
S/I	0.1455	likely_benign	0.1601	benign	-0.214	Destabilizing	0.524	D	0.553	neutral	None	None	None	None	N
S/K	0.6752	likely_pathogenic	0.7202	pathogenic	-0.578	Destabilizing	0.524	D	0.4	neutral	None	None	None	None	N
S/L	0.0977	likely_benign	0.11	benign	-0.214	Destabilizing	0.185	N	0.439	neutral	None	None	None	None	N
S/M	0.1676	likely_benign	0.1689	benign	0.031	Stabilizing	0.96	D	0.455	neutral	None	None	None	None	N
S/N	0.1008	likely_benign	0.1131	benign	-0.303	Destabilizing	0.524	D	0.404	neutral	None	None	None	None	N
S/P	0.1258	likely_benign	0.1138	benign	-0.271	Destabilizing	0.627	D	0.543	neutral	N	0.386714756	None	None	N
S/Q	0.4971	ambiguous	0.5214	ambiguous	-0.56	Destabilizing	0.887	D	0.444	neutral	None	None	None	None	N
S/R	0.6144	likely_pathogenic	0.6782	pathogenic	-0.346	Destabilizing	0.524	D	0.537	neutral	None	None	None	None	N
S/T	0.0643	likely_benign	0.0611	benign	-0.419	Destabilizing	0.005	N	0.211	neutral	N	0.441066529	None	None	N
S/V	0.145	likely_benign	0.1485	benign	-0.271	Destabilizing	0.185	N	0.439	neutral	None	None	None	None	N
S/W	0.437	ambiguous	0.5198	ambiguous	-0.894	Destabilizing	0.989	D	0.67	prob.neutral	None	None	None	None	N
S/Y	0.2175	likely_benign	0.2666	benign	-0.639	Destabilizing	0.947	D	0.525	neutral	N	0.461905948	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.