TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18920	56983;56984;56985	chr2:178598952;178598951;178598950	chr2:179463679;179463678;179463677
N2AB	17279	52060;52061;52062	chr2:178598952;178598951;178598950	chr2:179463679;179463678;179463677
N2A	16352	49279;49280;49281	chr2:178598952;178598951;178598950	chr2:179463679;179463678;179463677
N2B	9855	29788;29789;29790	chr2:178598952;178598951;178598950	chr2:179463679;179463678;179463677
Novex-1	9980	30163;30164;30165	chr2:178598952;178598951;178598950	chr2:179463679;179463678;179463677
Novex-2	10047	30364;30365;30366	chr2:178598952;178598951;178598950	chr2:179463679;179463678;179463677
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Fn3-25
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.133
• 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
W/R	rs1425662810	-1.767	0.999	N	0.801	0.427	0.60221348894	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.01E-06	0
W/R	rs1425662810	-1.767	0.999	N	0.801	0.427	0.60221348894	gnomAD-4.0.0	1.59347E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86043E-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
W/A	0.9707	likely_pathogenic	0.946	pathogenic	-3.118	Highly Destabilizing	0.998	D	0.721	prob.delet.	None	None	None	None	N
W/C	0.9112	likely_pathogenic	0.8778	pathogenic	-1.425	Destabilizing	1.0	D	0.753	deleterious	N	0.480557919	None	None	N
W/D	0.9967	likely_pathogenic	0.9925	pathogenic	-2.989	Highly Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
W/E	0.9931	likely_pathogenic	0.985	pathogenic	-2.885	Highly Destabilizing	0.999	D	0.79	deleterious	None	None	None	None	N
W/F	0.3332	likely_benign	0.3018	benign	-1.858	Destabilizing	0.171	N	0.394	neutral	None	None	None	None	N
W/G	0.9732	likely_pathogenic	0.9477	pathogenic	-3.334	Highly Destabilizing	0.999	D	0.672	neutral	N	0.469683263	None	None	N
W/H	0.8256	likely_pathogenic	0.7705	pathogenic	-2.02	Highly Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
W/I	0.7537	likely_pathogenic	0.6002	pathogenic	-2.289	Highly Destabilizing	0.996	D	0.759	deleterious	None	None	None	None	N
W/K	0.994	likely_pathogenic	0.9875	pathogenic	-2.062	Highly Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
W/L	0.7146	likely_pathogenic	0.577	pathogenic	-2.289	Highly Destabilizing	0.961	D	0.653	neutral	N	0.418834669	None	None	N
W/M	0.8838	likely_pathogenic	0.8101	pathogenic	-1.688	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
W/N	0.9796	likely_pathogenic	0.9671	pathogenic	-2.636	Highly Destabilizing	0.999	D	0.794	deleterious	None	None	None	None	N
W/P	0.9996	likely_pathogenic	0.999	pathogenic	-2.592	Highly Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
W/Q	0.9831	likely_pathogenic	0.9693	pathogenic	-2.559	Highly Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
W/R	0.9836	likely_pathogenic	0.9684	pathogenic	-1.659	Destabilizing	0.999	D	0.801	deleterious	N	0.431281105	None	None	N
W/S	0.9389	likely_pathogenic	0.8992	pathogenic	-2.862	Highly Destabilizing	0.999	D	0.767	deleterious	N	0.441594099	None	None	N
W/T	0.9544	likely_pathogenic	0.908	pathogenic	-2.698	Highly Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
W/V	0.8001	likely_pathogenic	0.6814	pathogenic	-2.592	Highly Destabilizing	0.996	D	0.728	prob.delet.	None	None	None	None	N
W/Y	0.4983	ambiguous	0.4342	ambiguous	-1.645	Destabilizing	0.971	D	0.623	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.