TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10069	30430;30431;30432	chr2:178704165;178704164;178704163	chr2:179568892;179568891;179568890
N2AB	9752	29479;29480;29481	chr2:178704165;178704164;178704163	chr2:179568892;179568891;179568890
N2A	8825	26698;26699;26700	chr2:178704165;178704164;178704163	chr2:179568892;179568891;179568890
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-85
• Domain position: 81
• Structural Position: 172
• Q(SASA): 0.1511
• 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	None	None	0.988	None	0.78	0.372	0.361958692863	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
A/T	rs1167245039	None	0.142	None	0.409	0.28	0.107399877778	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	2.07039E-04	0
A/T	rs1167245039	None	0.142	None	0.409	0.28	0.107399877778	gnomAD-4.0.0	1.31404E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46972E-05	2.07039E-04	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	0.8885	likely_pathogenic	0.9049	pathogenic	-1.254	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
A/D	0.9855	likely_pathogenic	0.9883	pathogenic	-1.917	Destabilizing	0.991	D	0.817	deleterious	None	None	None	None	N
A/E	0.9808	likely_pathogenic	0.9876	pathogenic	-1.955	Destabilizing	0.988	D	0.78	deleterious	None	None	None	None	N
A/F	0.9802	likely_pathogenic	0.9867	pathogenic	-1.248	Destabilizing	0.995	D	0.867	deleterious	None	None	None	None	N
A/G	0.3371	likely_benign	0.3598	ambiguous	-1.274	Destabilizing	0.958	D	0.601	neutral	None	None	None	None	N
A/H	0.9887	likely_pathogenic	0.99	pathogenic	-1.346	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
A/I	0.9717	likely_pathogenic	0.9828	pathogenic	-0.535	Destabilizing	0.991	D	0.819	deleterious	None	None	None	None	N
A/K	0.9889	likely_pathogenic	0.9911	pathogenic	-1.29	Destabilizing	0.991	D	0.781	deleterious	None	None	None	None	N
A/L	0.9141	likely_pathogenic	0.9442	pathogenic	-0.535	Destabilizing	0.938	D	0.667	neutral	None	None	None	None	N
A/M	0.9305	likely_pathogenic	0.9571	pathogenic	-0.483	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
A/N	0.9783	likely_pathogenic	0.9837	pathogenic	-1.132	Destabilizing	0.991	D	0.832	deleterious	None	None	None	None	N
A/P	0.9964	likely_pathogenic	0.9975	pathogenic	-0.663	Destabilizing	0.994	D	0.829	deleterious	None	None	None	None	N
A/Q	0.9671	likely_pathogenic	0.9742	pathogenic	-1.37	Destabilizing	0.995	D	0.852	deleterious	None	None	None	None	N
A/R	0.9615	likely_pathogenic	0.9679	pathogenic	-0.865	Destabilizing	0.991	D	0.837	deleterious	None	None	None	None	N
A/S	0.267	likely_benign	0.3012	benign	-1.416	Destabilizing	0.919	D	0.587	neutral	None	None	None	None	N
A/T	0.564	ambiguous	0.6762	pathogenic	-1.373	Destabilizing	0.142	N	0.409	neutral	None	None	None	None	N
A/V	0.8261	likely_pathogenic	0.8816	pathogenic	-0.663	Destabilizing	0.919	D	0.615	neutral	None	None	None	None	N
A/W	0.9974	likely_pathogenic	0.9983	pathogenic	-1.553	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
A/Y	0.9912	likely_pathogenic	0.9933	pathogenic	-1.164	Destabilizing	1.0	D	0.869	deleterious	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.