TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1113	3562;3563;3564	chr2:178782255;178782254;178782253	chr2:179646982;179646981;179646980
N2AB	1113	3562;3563;3564	chr2:178782255;178782254;178782253	chr2:179646982;179646981;179646980
N2A	1113	3562;3563;3564	chr2:178782255;178782254;178782253	chr2:179646982;179646981;179646980
N2B	1067	3424;3425;3426	chr2:178782255;178782254;178782253	chr2:179646982;179646981;179646980
Novex-1	1067	3424;3425;3426	chr2:178782255;178782254;178782253	chr2:179646982;179646981;179646980
Novex-2	1067	3424;3425;3426	chr2:178782255;178782254;178782253	chr2:179646982;179646981;179646980
Novex-3	1113	3562;3563;3564	chr2:178782255;178782254;178782253	chr2:179646982;179646981;179646980

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-4
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.1901
• 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/A	rs763409137	-2.252	0.822	D	0.646	0.681	0.732157991247	gnomAD-2.1.1	7.97E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.76E-05	0
V/A	rs763409137	-2.252	0.822	D	0.646	0.681	0.732157991247	gnomAD-4.0.0	1.02611E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.34895E-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
V/A	0.8061	likely_pathogenic	0.7692	pathogenic	-2.158	Highly Destabilizing	0.822	D	0.646	neutral	D	0.623861126	None	None	N
V/C	0.9371	likely_pathogenic	0.9231	pathogenic	-1.304	Destabilizing	0.998	D	0.699	prob.neutral	None	None	None	None	N
V/D	0.9975	likely_pathogenic	0.9965	pathogenic	-3.097	Highly Destabilizing	0.993	D	0.831	deleterious	None	None	None	None	N
V/E	0.9916	likely_pathogenic	0.9893	pathogenic	-2.871	Highly Destabilizing	0.99	D	0.827	deleterious	D	0.749827329	None	None	N
V/F	0.7124	likely_pathogenic	0.6593	pathogenic	-1.506	Destabilizing	0.956	D	0.738	prob.delet.	None	None	None	None	N
V/G	0.9331	likely_pathogenic	0.9129	pathogenic	-2.617	Highly Destabilizing	0.971	D	0.831	deleterious	D	0.749827329	None	None	N
V/H	0.9946	likely_pathogenic	0.9933	pathogenic	-2.392	Highly Destabilizing	0.998	D	0.806	deleterious	None	None	None	None	N
V/I	0.0908	likely_benign	0.0901	benign	-0.844	Destabilizing	0.006	N	0.184	neutral	N	0.467767293	None	None	N
V/K	0.9924	likely_pathogenic	0.9909	pathogenic	-1.829	Destabilizing	0.978	D	0.828	deleterious	None	None	None	None	N
V/L	0.5805	likely_pathogenic	0.5089	ambiguous	-0.844	Destabilizing	0.247	N	0.551	neutral	D	0.548439314	None	None	N
V/M	0.5883	likely_pathogenic	0.5496	ambiguous	-0.66	Destabilizing	0.956	D	0.697	prob.neutral	None	None	None	None	N
V/N	0.9893	likely_pathogenic	0.9871	pathogenic	-2.203	Highly Destabilizing	0.993	D	0.832	deleterious	None	None	None	None	N
V/P	0.9872	likely_pathogenic	0.9835	pathogenic	-1.264	Destabilizing	0.993	D	0.82	deleterious	None	None	None	None	N
V/Q	0.9857	likely_pathogenic	0.9834	pathogenic	-2.083	Highly Destabilizing	0.993	D	0.825	deleterious	None	None	None	None	N
V/R	0.9832	likely_pathogenic	0.9794	pathogenic	-1.632	Destabilizing	0.993	D	0.831	deleterious	None	None	None	None	N
V/S	0.9398	likely_pathogenic	0.931	pathogenic	-2.664	Highly Destabilizing	0.978	D	0.818	deleterious	None	None	None	None	N
V/T	0.8257	likely_pathogenic	0.8315	pathogenic	-2.324	Highly Destabilizing	0.86	D	0.717	prob.delet.	None	None	None	None	N
V/W	0.9939	likely_pathogenic	0.9915	pathogenic	-2.063	Highly Destabilizing	0.998	D	0.788	deleterious	None	None	None	None	N
V/Y	0.9746	likely_pathogenic	0.9671	pathogenic	-1.662	Destabilizing	0.978	D	0.722	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.