TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19063	57412;57413;57414	chr2:178597983;178597982;178597981	chr2:179462710;179462709;179462708
N2AB	17422	52489;52490;52491	chr2:178597983;178597982;178597981	chr2:179462710;179462709;179462708
N2A	16495	49708;49709;49710	chr2:178597983;178597982;178597981	chr2:179462710;179462709;179462708
N2B	9998	30217;30218;30219	chr2:178597983;178597982;178597981	chr2:179462710;179462709;179462708
Novex-1	10123	30592;30593;30594	chr2:178597983;178597982;178597981	chr2:179462710;179462709;179462708
Novex-2	10190	30793;30794;30795	chr2:178597983;178597982;178597981	chr2:179462710;179462709;179462708
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: Fn3-26
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.1146
• 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	None	None	0.997	N	0.606	0.394	0.731997862569	gnomAD-4.0.0	1.59213E-06	None	None	None	None	N	None	0	0	None	0	2.77809E-05	None	0	0	0	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	0.8948	likely_pathogenic	0.9024	pathogenic	-2.634	Highly Destabilizing	0.999	D	0.659	neutral	D	0.533223097	None	None	N
V/C	0.9605	likely_pathogenic	0.968	pathogenic	-2.105	Highly Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
V/D	0.9989	likely_pathogenic	0.9988	pathogenic	-3.366	Highly Destabilizing	1.0	D	0.839	deleterious	D	0.632037477	None	None	N
V/E	0.9962	likely_pathogenic	0.9958	pathogenic	-3.091	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
V/F	0.961	likely_pathogenic	0.9595	pathogenic	-1.356	Destabilizing	1.0	D	0.737	prob.delet.	D	0.551327352	None	None	N
V/G	0.9361	likely_pathogenic	0.9292	pathogenic	-3.138	Highly Destabilizing	1.0	D	0.826	deleterious	D	0.632037477	None	None	N
V/H	0.9992	likely_pathogenic	0.9992	pathogenic	-2.814	Highly Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
V/I	0.1235	likely_benign	0.1308	benign	-1.153	Destabilizing	0.997	D	0.606	neutral	N	0.517767592	None	None	N
V/K	0.9971	likely_pathogenic	0.9966	pathogenic	-2.152	Highly Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
V/L	0.8455	likely_pathogenic	0.86	pathogenic	-1.153	Destabilizing	0.997	D	0.679	prob.neutral	N	0.502340051	None	None	N
V/M	0.9071	likely_pathogenic	0.9133	pathogenic	-1.503	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
V/N	0.9958	likely_pathogenic	0.9956	pathogenic	-2.696	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
V/P	0.9963	likely_pathogenic	0.9971	pathogenic	-1.634	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
V/Q	0.9955	likely_pathogenic	0.9951	pathogenic	-2.398	Highly Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
V/R	0.9936	likely_pathogenic	0.9926	pathogenic	-2.076	Highly Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
V/S	0.9755	likely_pathogenic	0.9738	pathogenic	-3.159	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
V/T	0.9387	likely_pathogenic	0.9347	pathogenic	-2.764	Highly Destabilizing	0.999	D	0.659	neutral	None	None	None	None	N
V/W	0.9992	likely_pathogenic	0.9993	pathogenic	-1.853	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
V/Y	0.9963	likely_pathogenic	0.9963	pathogenic	-1.688	Destabilizing	1.0	D	0.739	prob.delet.	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.