TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35764	107515;107516;107517	chr2:178528361;178528360;178528359	chr2:179393088;179393087;179393086
N2AB	34123	102592;102593;102594	chr2:178528361;178528360;178528359	chr2:179393088;179393087;179393086
N2A	33196	99811;99812;99813	chr2:178528361;178528360;178528359	chr2:179393088;179393087;179393086
N2B	26699	80320;80321;80322	chr2:178528361;178528360;178528359	chr2:179393088;179393087;179393086
Novex-1	26824	80695;80696;80697	chr2:178528361;178528360;178528359	chr2:179393088;179393087;179393086
Novex-2	26891	80896;80897;80898	chr2:178528361;178528360;178528359	chr2:179393088;179393087;179393086
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-168
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.312
• 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/S	rs879048717	-0.854	0.998	N	0.663	0.433	0.338592109245	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
A/S	rs879048717	-0.854	0.998	N	0.663	0.433	0.338592109245	gnomAD-4.0.0	1.71041E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.24855E-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
A/C	0.7275	likely_pathogenic	0.7475	pathogenic	-2.036	Highly Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
A/D	0.9733	likely_pathogenic	0.9773	pathogenic	-2.831	Highly Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
A/E	0.9645	likely_pathogenic	0.9675	pathogenic	-2.763	Highly Destabilizing	1.0	D	0.805	deleterious	N	0.510173956	None	None	N
A/F	0.9211	likely_pathogenic	0.9223	pathogenic	-1.244	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
A/G	0.4199	ambiguous	0.416	ambiguous	-1.56	Destabilizing	0.999	D	0.658	neutral	N	0.498564161	None	None	N
A/H	0.9789	likely_pathogenic	0.9811	pathogenic	-1.565	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
A/I	0.5222	ambiguous	0.5745	pathogenic	-0.458	Destabilizing	0.994	D	0.725	prob.delet.	None	None	None	None	N
A/K	0.9849	likely_pathogenic	0.987	pathogenic	-1.537	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
A/L	0.5857	likely_pathogenic	0.6014	pathogenic	-0.458	Destabilizing	0.994	D	0.607	neutral	None	None	None	None	N
A/M	0.7052	likely_pathogenic	0.725	pathogenic	-0.756	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
A/N	0.9125	likely_pathogenic	0.9258	pathogenic	-1.765	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
A/P	0.784	likely_pathogenic	0.8037	pathogenic	-0.681	Destabilizing	1.0	D	0.785	deleterious	N	0.500240624	None	None	N
A/Q	0.956	likely_pathogenic	0.9612	pathogenic	-1.866	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
A/R	0.9655	likely_pathogenic	0.9684	pathogenic	-1.242	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
A/S	0.2145	likely_benign	0.2409	benign	-2.094	Highly Destabilizing	0.998	D	0.663	neutral	N	0.496314884	None	None	N
A/T	0.1475	likely_benign	0.1588	benign	-1.927	Destabilizing	0.996	D	0.727	prob.delet.	N	0.440288243	None	None	N
A/V	0.2213	likely_benign	0.2414	benign	-0.681	Destabilizing	0.884	D	0.387	neutral	N	0.373460244	None	None	N
A/W	0.9941	likely_pathogenic	0.9947	pathogenic	-1.693	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
A/Y	0.9749	likely_pathogenic	0.9758	pathogenic	-1.253	Destabilizing	1.0	D	0.761	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.