TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1872	5839;5840;5841	chr2:178776250;178776249;178776248	chr2:179640977;179640976;179640975
N2AB	1872	5839;5840;5841	chr2:178776250;178776249;178776248	chr2:179640977;179640976;179640975
N2A	1872	5839;5840;5841	chr2:178776250;178776249;178776248	chr2:179640977;179640976;179640975
N2B	1826	5701;5702;5703	chr2:178776250;178776249;178776248	chr2:179640977;179640976;179640975
Novex-1	1826	5701;5702;5703	chr2:178776250;178776249;178776248	chr2:179640977;179640976;179640975
Novex-2	1826	5701;5702;5703	chr2:178776250;178776249;178776248	chr2:179640977;179640976;179640975
Novex-3	1872	5839;5840;5841	chr2:178776250;178776249;178776248	chr2:179640977;179640976;179640975

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-9
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.2034
• Predicted PPI site: I

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/L	None	None	0.039	D	0.309	0.286	0.332902724076	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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	0.9203	likely_pathogenic	0.9206	pathogenic	-1.653	Destabilizing	0.928	D	0.64	neutral	D	0.68596939	None	None	I
V/C	0.9776	likely_pathogenic	0.9783	pathogenic	-0.808	Destabilizing	0.999	D	0.748	deleterious	None	None	None	None	I
V/D	0.9982	likely_pathogenic	0.9981	pathogenic	-1.818	Destabilizing	0.996	D	0.833	deleterious	D	0.780824125	None	None	I
V/E	0.9912	likely_pathogenic	0.99	pathogenic	-1.796	Destabilizing	0.992	D	0.833	deleterious	None	None	None	None	I
V/F	0.9365	likely_pathogenic	0.9168	pathogenic	-1.288	Destabilizing	0.957	D	0.772	deleterious	D	0.631720315	None	None	I
V/G	0.9593	likely_pathogenic	0.9581	pathogenic	-1.994	Destabilizing	0.989	D	0.839	deleterious	D	0.744625307	None	None	I
V/H	0.9982	likely_pathogenic	0.9979	pathogenic	-1.685	Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	I
V/I	0.12	likely_benign	0.1074	benign	-0.79	Destabilizing	0.726	D	0.594	neutral	N	0.516348527	None	None	I
V/K	0.9939	likely_pathogenic	0.9931	pathogenic	-1.411	Destabilizing	0.992	D	0.832	deleterious	None	None	None	None	I
V/L	0.6532	likely_pathogenic	0.6281	pathogenic	-0.79	Destabilizing	0.039	N	0.309	neutral	D	0.549750545	None	None	I
V/M	0.7351	likely_pathogenic	0.6981	pathogenic	-0.451	Destabilizing	0.983	D	0.729	prob.delet.	None	None	None	None	I
V/N	0.9925	likely_pathogenic	0.9917	pathogenic	-1.123	Destabilizing	0.997	D	0.847	deleterious	None	None	None	None	I
V/P	0.9921	likely_pathogenic	0.993	pathogenic	-1.046	Destabilizing	0.997	D	0.834	deleterious	None	None	None	None	I
V/Q	0.9926	likely_pathogenic	0.9916	pathogenic	-1.27	Destabilizing	0.997	D	0.843	deleterious	None	None	None	None	I
V/R	0.9923	likely_pathogenic	0.9914	pathogenic	-0.91	Destabilizing	0.992	D	0.843	deleterious	None	None	None	None	I
V/S	0.983	likely_pathogenic	0.9823	pathogenic	-1.556	Destabilizing	0.992	D	0.833	deleterious	None	None	None	None	I
V/T	0.9052	likely_pathogenic	0.9072	pathogenic	-1.43	Destabilizing	0.944	D	0.685	prob.neutral	None	None	None	None	I
V/W	0.9983	likely_pathogenic	0.9977	pathogenic	-1.563	Destabilizing	0.999	D	0.828	deleterious	None	None	None	None	I
V/Y	0.9939	likely_pathogenic	0.9922	pathogenic	-1.286	Destabilizing	0.992	D	0.768	deleterious	None	None	None	None	I

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.