TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6745	20458;20459;20460	chr2:178727132;178727131;178727130	chr2:179591859;179591858;179591857
N2AB	6428	19507;19508;19509	chr2:178727132;178727131;178727130	chr2:179591859;179591858;179591857
N2A	5501	16726;16727;16728	chr2:178727132;178727131;178727130	chr2:179591859;179591858;179591857
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: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-51
• Domain position: 79
• Structural Position: 162
• Q(SASA): 0.7755
• 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
P/S	rs756864644	-0.098	0.801	N	0.351	0.199	0.264547087235	gnomAD-2.1.1	2.87E-05	None	None	None	None	I	None	0	0	None	0	0	None	2.36423E-04	None	0	0	0
P/S	rs756864644	-0.098	0.801	N	0.351	0.199	0.264547087235	gnomAD-4.0.0	1.45056E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.06541E-07	2.38983E-04	0
P/T	None	None	0.891	N	0.362	0.205	0.465975295344	gnomAD-4.0.0	6.90741E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.06541E-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
P/A	0.0752	likely_benign	0.083	benign	-0.375	Destabilizing	0.801	D	0.355	neutral	N	0.407170173	None	None	I
P/C	0.5712	likely_pathogenic	0.6395	pathogenic	-0.709	Destabilizing	0.998	D	0.494	neutral	None	None	None	None	I
P/D	0.2489	likely_benign	0.2746	benign	-0.431	Destabilizing	0.007	N	0.194	neutral	None	None	None	None	I
P/E	0.184	likely_benign	0.206	benign	-0.556	Destabilizing	0.029	N	0.199	neutral	None	None	None	None	I
P/F	0.3775	ambiguous	0.4372	ambiguous	-0.726	Destabilizing	0.991	D	0.427	neutral	None	None	None	None	I
P/G	0.2816	likely_benign	0.3206	benign	-0.456	Destabilizing	0.842	D	0.392	neutral	None	None	None	None	I
P/H	0.1591	likely_benign	0.1842	benign	-0.045	Destabilizing	0.989	D	0.425	neutral	N	0.497272102	None	None	I
P/I	0.2229	likely_benign	0.2561	benign	-0.313	Destabilizing	0.974	D	0.425	neutral	None	None	None	None	I
P/K	0.2307	likely_benign	0.2781	benign	-0.43	Destabilizing	0.842	D	0.341	neutral	None	None	None	None	I
P/L	0.1013	likely_benign	0.1117	benign	-0.313	Destabilizing	0.966	D	0.392	neutral	N	0.478166267	None	None	I
P/M	0.2554	likely_benign	0.2885	benign	-0.464	Destabilizing	0.998	D	0.44	neutral	None	None	None	None	I
P/N	0.2319	likely_benign	0.2677	benign	-0.21	Destabilizing	0.728	D	0.38	neutral	None	None	None	None	I
P/Q	0.1432	likely_benign	0.162	benign	-0.457	Destabilizing	0.949	D	0.343	neutral	None	None	None	None	I
P/R	0.1541	likely_benign	0.1787	benign	0.086	Stabilizing	0.934	D	0.41	neutral	N	0.466871838	None	None	I
P/S	0.1064	likely_benign	0.1205	benign	-0.504	Destabilizing	0.801	D	0.351	neutral	N	0.445973703	None	None	I
P/T	0.0869	likely_benign	0.0963	benign	-0.536	Destabilizing	0.891	D	0.362	neutral	N	0.47539532	None	None	I
P/V	0.1678	likely_benign	0.19	benign	-0.302	Destabilizing	0.974	D	0.395	neutral	None	None	None	None	I
P/W	0.5432	ambiguous	0.6217	pathogenic	-0.794	Destabilizing	0.998	D	0.571	neutral	None	None	None	None	I
P/Y	0.3474	ambiguous	0.4103	ambiguous	-0.506	Destabilizing	0.991	D	0.425	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.