TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20465	61618;61619;61620	chr2:178590332;178590331;178590330	chr2:179455059;179455058;179455057
N2AB	18824	56695;56696;56697	chr2:178590332;178590331;178590330	chr2:179455059;179455058;179455057
N2A	17897	53914;53915;53916	chr2:178590332;178590331;178590330	chr2:179455059;179455058;179455057
N2B	11400	34423;34424;34425	chr2:178590332;178590331;178590330	chr2:179455059;179455058;179455057
Novex-1	11525	34798;34799;34800	chr2:178590332;178590331;178590330	chr2:179455059;179455058;179455057
Novex-2	11592	34999;35000;35001	chr2:178590332;178590331;178590330	chr2:179455059;179455058;179455057
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-36
• Domain position: 95
• Structural Position: 127
• Q(SASA): 0.1797
• 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/M	rs1358181606	None	0.999	N	0.721	0.294	0.267755039894	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	1.47E-05	0	9.59693E-04
V/M	rs1358181606	None	0.999	N	0.721	0.294	0.267755039894	gnomAD-4.0.0	2.63071E-05	None	None	None	None	N	None	0	6.56254E-05	None	0	0	None	0	0	1.47076E-05	0	9.59693E-04

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	0.5956	likely_pathogenic	0.4808	ambiguous	-1.601	Destabilizing	0.996	D	0.555	neutral	N	0.480735356	None	None	N
V/C	0.8876	likely_pathogenic	0.8555	pathogenic	-1.045	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
V/D	0.9673	likely_pathogenic	0.8942	pathogenic	-1.739	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
V/E	0.9209	likely_pathogenic	0.8159	pathogenic	-1.517	Destabilizing	1.0	D	0.881	deleterious	N	0.482509783	None	None	N
V/F	0.4898	ambiguous	0.3332	benign	-0.882	Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
V/G	0.805	likely_pathogenic	0.6509	pathogenic	-2.123	Highly Destabilizing	1.0	D	0.902	deleterious	N	0.482509783	None	None	N
V/H	0.9698	likely_pathogenic	0.9262	pathogenic	-1.72	Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
V/I	0.0877	likely_benign	0.09	benign	-0.16	Destabilizing	0.668	D	0.245	neutral	None	None	None	None	N
V/K	0.9535	likely_pathogenic	0.8812	pathogenic	-1.214	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
V/L	0.4551	ambiguous	0.3524	ambiguous	-0.16	Destabilizing	0.959	D	0.583	neutral	N	0.512677832	None	None	N
V/M	0.3856	ambiguous	0.3038	benign	-0.216	Destabilizing	0.999	D	0.721	deleterious	N	0.482509783	None	None	N
V/N	0.9162	likely_pathogenic	0.8218	pathogenic	-1.539	Destabilizing	1.0	D	0.918	deleterious	None	None	None	None	N
V/P	0.9637	likely_pathogenic	0.9234	pathogenic	-0.612	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
V/Q	0.9106	likely_pathogenic	0.825	pathogenic	-1.35	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
V/R	0.9376	likely_pathogenic	0.85	pathogenic	-1.16	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
V/S	0.8329	likely_pathogenic	0.7004	pathogenic	-2.193	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
V/T	0.5973	likely_pathogenic	0.482	ambiguous	-1.811	Destabilizing	0.997	D	0.611	neutral	None	None	None	None	N
V/W	0.9808	likely_pathogenic	0.9514	pathogenic	-1.307	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
V/Y	0.9195	likely_pathogenic	0.8314	pathogenic	-0.871	Destabilizing	1.0	D	0.821	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.