TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4821	14686;14687;14688	chr2:178735985;178735984;178735983	chr2:179600712;179600711;179600710
N2AB	4504	13735;13736;13737	chr2:178735985;178735984;178735983	chr2:179600712;179600711;179600710
N2A	3577	10954;10955;10956	chr2:178735985;178735984;178735983	chr2:179600712;179600711;179600710
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-31
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.4643
• 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
T/I	rs1358712791	None	0.994	N	0.486	0.478	0.723311353475	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs1358712791	None	0.994	N	0.486	0.478	0.723311353475	gnomAD-4.0.0	6.57013E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.46959E-05	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
T/A	0.1534	likely_benign	0.1662	benign	-0.637	Destabilizing	0.835	D	0.44	neutral	N	0.482615575	None	None	I
T/C	0.6486	likely_pathogenic	0.6849	pathogenic	-0.438	Destabilizing	1.0	D	0.527	neutral	None	None	None	None	I
T/D	0.5247	ambiguous	0.6023	pathogenic	0.135	Stabilizing	0.97	D	0.504	neutral	None	None	None	None	I
T/E	0.465	ambiguous	0.5294	ambiguous	0.134	Stabilizing	0.97	D	0.519	neutral	None	None	None	None	I
T/F	0.2762	likely_benign	0.3469	ambiguous	-0.857	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	I
T/G	0.4611	ambiguous	0.5026	ambiguous	-0.853	Destabilizing	0.97	D	0.585	neutral	None	None	None	None	I
T/H	0.3314	likely_benign	0.3805	ambiguous	-0.963	Destabilizing	1.0	D	0.658	neutral	None	None	None	None	I
T/I	0.2527	likely_benign	0.2917	benign	-0.159	Destabilizing	0.994	D	0.486	neutral	N	0.400227618	None	None	I
T/K	0.2913	likely_benign	0.3614	ambiguous	-0.516	Destabilizing	0.97	D	0.508	neutral	None	None	None	None	I
T/L	0.1597	likely_benign	0.1691	benign	-0.159	Destabilizing	0.985	D	0.491	neutral	None	None	None	None	I
T/M	0.1112	likely_benign	0.1129	benign	-0.219	Destabilizing	1.0	D	0.509	neutral	None	None	None	None	I
T/N	0.1456	likely_benign	0.1757	benign	-0.432	Destabilizing	0.961	D	0.487	neutral	N	0.448261878	None	None	I
T/P	0.4404	ambiguous	0.4765	ambiguous	-0.287	Destabilizing	0.994	D	0.488	neutral	N	0.512215485	None	None	I
T/Q	0.3098	likely_benign	0.3665	ambiguous	-0.505	Destabilizing	0.996	D	0.501	neutral	None	None	None	None	I
T/R	0.2687	likely_benign	0.3329	benign	-0.297	Destabilizing	0.996	D	0.503	neutral	None	None	None	None	I
T/S	0.1218	likely_benign	0.1481	benign	-0.693	Destabilizing	0.287	N	0.221	neutral	N	0.454939649	None	None	I
T/V	0.2253	likely_benign	0.2481	benign	-0.287	Destabilizing	0.985	D	0.45	neutral	None	None	None	None	I
T/W	0.6648	likely_pathogenic	0.7354	pathogenic	-0.883	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
T/Y	0.3037	likely_benign	0.3728	ambiguous	-0.607	Destabilizing	0.999	D	0.653	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.