TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7333	22222;22223;22224	chr2:178722902;178722901;178722900	chr2:179587629;179587628;179587627
N2AB	7016	21271;21272;21273	chr2:178722902;178722901;178722900	chr2:179587629;179587628;179587627
N2A	6089	18490;18491;18492	chr2:178722902;178722901;178722900	chr2:179587629;179587628;179587627
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-58
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.3595
• Predicted PPI site: I

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
E/G	None	None	0.997	N	0.486	0.487	None	gnomAD-4.0.0	1.59401E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86248E-06	0	0
E/Q	None	None	0.999	N	0.479	0.288	0.312608672186	gnomAD-4.0.0	1.59407E-06	None	None	None	None	I	None	0	0	None	0	2.78056E-05	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
E/A	0.116	likely_benign	0.1632	benign	-0.584	Destabilizing	0.983	D	0.359	neutral	N	0.480534568	None	None	I
E/C	0.7382	likely_pathogenic	0.8436	pathogenic	-0.355	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
E/D	0.13	likely_benign	0.1731	benign	-0.695	Destabilizing	0.045	N	0.22	neutral	N	0.512916345	None	None	I
E/F	0.5438	ambiguous	0.6652	pathogenic	-0.042	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
E/G	0.1609	likely_benign	0.2473	benign	-0.881	Destabilizing	0.997	D	0.486	neutral	N	0.488685432	None	None	I
E/H	0.29	likely_benign	0.3843	ambiguous	0.05	Stabilizing	1.0	D	0.503	neutral	None	None	None	None	I
E/I	0.2122	likely_benign	0.2861	benign	0.203	Stabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	I
E/K	0.1165	likely_benign	0.1586	benign	-0.072	Destabilizing	0.995	D	0.375	neutral	N	0.486479106	None	None	I
E/L	0.2199	likely_benign	0.3184	benign	0.203	Stabilizing	0.999	D	0.662	neutral	None	None	None	None	I
E/M	0.3052	likely_benign	0.4075	ambiguous	0.31	Stabilizing	0.999	D	0.637	neutral	None	None	None	None	I
E/N	0.2145	likely_benign	0.2998	benign	-0.6	Destabilizing	0.984	D	0.432	neutral	None	None	None	None	I
E/P	0.5004	ambiguous	0.6908	pathogenic	-0.038	Destabilizing	0.998	D	0.586	neutral	None	None	None	None	I
E/Q	0.1024	likely_benign	0.1245	benign	-0.504	Destabilizing	0.999	D	0.479	neutral	N	0.481054643	None	None	I
E/R	0.1886	likely_benign	0.2482	benign	0.292	Stabilizing	1.0	D	0.513	neutral	None	None	None	None	I
E/S	0.1592	likely_benign	0.2185	benign	-0.807	Destabilizing	0.857	D	0.291	neutral	None	None	None	None	I
E/T	0.1479	likely_benign	0.2015	benign	-0.558	Destabilizing	0.995	D	0.459	neutral	None	None	None	None	I
E/V	0.1196	likely_benign	0.1559	benign	-0.038	Destabilizing	0.998	D	0.612	neutral	N	0.452654533	None	None	I
E/W	0.7499	likely_pathogenic	0.8455	pathogenic	0.236	Stabilizing	1.0	D	0.667	neutral	None	None	None	None	I
E/Y	0.4429	ambiguous	0.5653	pathogenic	0.23	Stabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	I

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.