TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6627	20104;20105;20106	chr2:178727699;178727698;178727697	chr2:179592426;179592425;179592424
N2AB	6310	19153;19154;19155	chr2:178727699;178727698;178727697	chr2:179592426;179592425;179592424
N2A	5383	16372;16373;16374	chr2:178727699;178727698;178727697	chr2:179592426;179592425;179592424
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: TCG
• RefSeq wild type template codon: AGC
• Domain: Ig-50
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.4654
• 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	rs773143754	-0.162	0.037	N	0.307	0.259	None	gnomAD-2.1.1	1.43E-05	None	None	None	None	N	None	0	5.66E-05	None	0	1.02491E-04	None	0	None	0	0	0
S/L	rs773143754	-0.162	0.037	N	0.307	0.259	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.93424E-04	None	0	0	0	0	0
S/L	rs773143754	-0.162	0.037	N	0.307	0.259	None	gnomAD-4.0.0	9.919E-06	None	None	None	None	N	None	0	1.66761E-05	None	0	2.22975E-05	None	0	0	2.54363E-06	8.7885E-05	4.80507E-05

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	0.0932	likely_benign	0.0915	benign	-0.513	Destabilizing	0.028	N	0.164	neutral	D	0.525957427	None	None	N
S/C	0.1693	likely_benign	0.1698	benign	-0.318	Destabilizing	0.993	D	0.475	neutral	None	None	None	None	N
S/D	0.2966	likely_benign	0.3056	benign	0.896	Stabilizing	0.932	D	0.392	neutral	None	None	None	None	N
S/E	0.415	ambiguous	0.4183	ambiguous	0.883	Stabilizing	0.932	D	0.303	neutral	None	None	None	None	N
S/F	0.1986	likely_benign	0.1992	benign	-0.929	Destabilizing	0.96	D	0.516	neutral	None	None	None	None	N
S/G	0.1029	likely_benign	0.1082	benign	-0.704	Destabilizing	0.737	D	0.303	neutral	None	None	None	None	N
S/H	0.3467	ambiguous	0.3757	ambiguous	-1.03	Destabilizing	0.998	D	0.478	neutral	None	None	None	None	N
S/I	0.2073	likely_benign	0.2012	benign	-0.121	Destabilizing	0.773	D	0.46	neutral	None	None	None	None	N
S/K	0.5661	likely_pathogenic	0.5828	pathogenic	-0.043	Destabilizing	0.932	D	0.297	neutral	None	None	None	None	N
S/L	0.1038	likely_benign	0.0967	benign	-0.121	Destabilizing	0.037	N	0.307	neutral	N	0.493829152	None	None	N
S/M	0.2137	likely_benign	0.2091	benign	-0.134	Destabilizing	0.38	N	0.316	neutral	None	None	None	None	N
S/N	0.1096	likely_benign	0.1202	benign	-0.024	Destabilizing	0.932	D	0.412	neutral	None	None	None	None	N
S/P	0.1672	likely_benign	0.1748	benign	-0.22	Destabilizing	0.973	D	0.485	neutral	N	0.485176259	None	None	N
S/Q	0.4309	ambiguous	0.453	ambiguous	-0.074	Destabilizing	0.98	D	0.458	neutral	None	None	None	None	N
S/R	0.509	ambiguous	0.5253	ambiguous	-0.058	Destabilizing	0.98	D	0.486	neutral	None	None	None	None	N
S/T	0.0921	likely_benign	0.0883	benign	-0.15	Destabilizing	0.064	N	0.163	neutral	N	0.462871527	None	None	N
S/V	0.2093	likely_benign	0.2069	benign	-0.22	Destabilizing	0.584	D	0.477	neutral	None	None	None	None	N
S/W	0.3437	ambiguous	0.3655	ambiguous	-0.925	Destabilizing	0.999	D	0.545	neutral	N	0.492266603	None	None	N
S/Y	0.1673	likely_benign	0.1719	benign	-0.6	Destabilizing	0.993	D	0.537	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.