TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21308	64147;64148;64149	chr2:178587289;178587288;178587287	chr2:179452016;179452015;179452014
N2AB	19667	59224;59225;59226	chr2:178587289;178587288;178587287	chr2:179452016;179452015;179452014
N2A	18740	56443;56444;56445	chr2:178587289;178587288;178587287	chr2:179452016;179452015;179452014
N2B	12243	36952;36953;36954	chr2:178587289;178587288;178587287	chr2:179452016;179452015;179452014
Novex-1	12368	37327;37328;37329	chr2:178587289;178587288;178587287	chr2:179452016;179452015;179452014
Novex-2	12435	37528;37529;37530	chr2:178587289;178587288;178587287	chr2:179452016;179452015;179452014
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-42
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.2036
• 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
A/E	rs772717263	None	0.949	N	0.526	0.325	0.308904156042	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/E	rs772717263	None	0.949	N	0.526	0.325	0.308904156042	gnomAD-4.0.0	4.06057E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.82002E-06	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
A/C	0.416	ambiguous	0.4316	ambiguous	-0.712	Destabilizing	0.996	D	0.599	neutral	None	None	None	None	N
A/D	0.5097	ambiguous	0.4834	ambiguous	-1.311	Destabilizing	0.987	D	0.637	neutral	None	None	None	None	N
A/E	0.3905	ambiguous	0.3614	ambiguous	-1.333	Destabilizing	0.949	D	0.526	neutral	N	0.434420197	None	None	N
A/F	0.3887	ambiguous	0.3871	ambiguous	-1.024	Destabilizing	0.923	D	0.644	neutral	None	None	None	None	N
A/G	0.134	likely_benign	0.1318	benign	-1.27	Destabilizing	0.84	D	0.537	neutral	N	0.44800557	None	None	N
A/H	0.5702	likely_pathogenic	0.5539	ambiguous	-1.421	Destabilizing	0.996	D	0.647	neutral	None	None	None	None	N
A/I	0.1503	likely_benign	0.161	benign	-0.416	Destabilizing	0.372	N	0.511	neutral	None	None	None	None	N
A/K	0.4594	ambiguous	0.4005	ambiguous	-1.289	Destabilizing	0.961	D	0.525	neutral	None	None	None	None	N
A/L	0.1527	likely_benign	0.1573	benign	-0.416	Destabilizing	0.415	N	0.509	neutral	None	None	None	None	N
A/M	0.1428	likely_benign	0.1545	benign	-0.253	Destabilizing	0.923	D	0.595	neutral	None	None	None	None	N
A/N	0.299	likely_benign	0.3095	benign	-0.919	Destabilizing	0.987	D	0.643	neutral	None	None	None	None	N
A/P	0.3517	ambiguous	0.3434	ambiguous	-0.571	Destabilizing	0.983	D	0.579	neutral	N	0.435441705	None	None	N
A/Q	0.3907	ambiguous	0.3726	ambiguous	-1.082	Destabilizing	0.987	D	0.589	neutral	None	None	None	None	N
A/R	0.4657	ambiguous	0.4099	ambiguous	-0.897	Destabilizing	0.961	D	0.592	neutral	None	None	None	None	N
A/S	0.1033	likely_benign	0.1033	benign	-1.251	Destabilizing	0.722	D	0.557	neutral	N	0.392920292	None	None	N
A/T	0.0857	likely_benign	0.09	benign	-1.188	Destabilizing	0.722	D	0.537	neutral	N	0.423819202	None	None	N
A/V	0.0865	likely_benign	0.0899	benign	-0.571	Destabilizing	0.003	N	0.253	neutral	N	0.38953327	None	None	N
A/W	0.7622	likely_pathogenic	0.7528	pathogenic	-1.39	Destabilizing	0.996	D	0.674	neutral	None	None	None	None	N
A/Y	0.5157	ambiguous	0.5164	ambiguous	-1.007	Destabilizing	0.961	D	0.649	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.