TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15519	46780;46781;46782	chr2:178619762;178619761;178619760	chr2:179484489;179484488;179484487
N2AB	13878	41857;41858;41859	chr2:178619762;178619761;178619760	chr2:179484489;179484488;179484487
N2A	12951	39076;39077;39078	chr2:178619762;178619761;178619760	chr2:179484489;179484488;179484487
N2B	6454	19585;19586;19587	chr2:178619762;178619761;178619760	chr2:179484489;179484488;179484487
Novex-1	6579	19960;19961;19962	chr2:178619762;178619761;178619760	chr2:179484489;179484488;179484487
Novex-2	6646	20161;20162;20163	chr2:178619762;178619761;178619760	chr2:179484489;179484488;179484487
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-107
• Domain position: 40
• Structural Position: 58
• Q(SASA): 0.247
• 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
V/I	rs1277355095	-0.782	None	N	0.214	0.094	0.253205268125	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
V/I	rs1277355095	-0.782	None	N	0.214	0.094	0.253205268125	gnomAD-4.0.0	1.36941E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80012E-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
V/A	0.702	likely_pathogenic	0.7481	pathogenic	-1.932	Destabilizing	0.104	N	0.567	neutral	N	0.514535014	None	None	N
V/C	0.9204	likely_pathogenic	0.9562	pathogenic	-1.168	Destabilizing	0.968	D	0.701	prob.neutral	None	None	None	None	N
V/D	0.9875	likely_pathogenic	0.9865	pathogenic	-2.49	Highly Destabilizing	0.667	D	0.804	deleterious	N	0.517721271	None	None	N
V/E	0.9663	likely_pathogenic	0.9643	pathogenic	-2.336	Highly Destabilizing	0.726	D	0.742	deleterious	None	None	None	None	N
V/F	0.6225	likely_pathogenic	0.5971	pathogenic	-1.316	Destabilizing	0.497	N	0.724	prob.delet.	N	0.514724825	None	None	N
V/G	0.9095	likely_pathogenic	0.9131	pathogenic	-2.381	Highly Destabilizing	0.667	D	0.773	deleterious	N	0.516904699	None	None	N
V/H	0.985	likely_pathogenic	0.987	pathogenic	-2.087	Highly Destabilizing	0.968	D	0.8	deleterious	None	None	None	None	N
V/I	0.0537	likely_benign	0.0635	benign	-0.71	Destabilizing	None	N	0.214	neutral	N	0.423920056	None	None	N
V/K	0.977	likely_pathogenic	0.9764	pathogenic	-1.702	Destabilizing	0.726	D	0.745	deleterious	None	None	None	None	N
V/L	0.2572	likely_benign	0.2958	benign	-0.71	Destabilizing	0.009	N	0.394	neutral	N	0.411097736	None	None	N
V/M	0.3511	ambiguous	0.4166	ambiguous	-0.496	Destabilizing	0.567	D	0.609	neutral	None	None	None	None	N
V/N	0.9477	likely_pathogenic	0.9588	pathogenic	-1.794	Destabilizing	0.89	D	0.817	deleterious	None	None	None	None	N
V/P	0.9306	likely_pathogenic	0.9457	pathogenic	-1.09	Destabilizing	0.89	D	0.759	deleterious	None	None	None	None	N
V/Q	0.9658	likely_pathogenic	0.9658	pathogenic	-1.767	Destabilizing	0.89	D	0.765	deleterious	None	None	None	None	N
V/R	0.9635	likely_pathogenic	0.9604	pathogenic	-1.389	Destabilizing	0.726	D	0.817	deleterious	None	None	None	None	N
V/S	0.8957	likely_pathogenic	0.9116	pathogenic	-2.297	Highly Destabilizing	0.726	D	0.692	prob.neutral	None	None	None	None	N
V/T	0.7228	likely_pathogenic	0.7646	pathogenic	-2.018	Highly Destabilizing	0.272	N	0.546	neutral	None	None	None	None	N
V/W	0.9843	likely_pathogenic	0.9848	pathogenic	-1.768	Destabilizing	0.968	D	0.758	deleterious	None	None	None	None	N
V/Y	0.9553	likely_pathogenic	0.9568	pathogenic	-1.385	Destabilizing	0.726	D	0.742	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.