TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25123	75592;75593;75594	chr2:178570765;178570764;178570763	chr2:179435492;179435491;179435490
N2AB	23482	70669;70670;70671	chr2:178570765;178570764;178570763	chr2:179435492;179435491;179435490
N2A	22555	67888;67889;67890	chr2:178570765;178570764;178570763	chr2:179435492;179435491;179435490
N2B	16058	48397;48398;48399	chr2:178570765;178570764;178570763	chr2:179435492;179435491;179435490
Novex-1	16183	48772;48773;48774	chr2:178570765;178570764;178570763	chr2:179435492;179435491;179435490
Novex-2	16250	48973;48974;48975	chr2:178570765;178570764;178570763	chr2:179435492;179435491;179435490
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-134
• Domain position: 13
• Structural Position: 16
• Q(SASA): 0.1596
• 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	rs1456861699	None	0.22	D	0.445	0.369	0.647442735181	gnomAD-4.0.0	2.73714E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59826E-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	0.4431	ambiguous	0.4802	ambiguous	-2.021	Highly Destabilizing	0.22	N	0.445	neutral	D	0.535139844	None	None	N
V/C	0.7218	likely_pathogenic	0.7597	pathogenic	-1.38	Destabilizing	0.968	D	0.533	neutral	None	None	None	None	N
V/D	0.9259	likely_pathogenic	0.9474	pathogenic	-2.43	Highly Destabilizing	0.667	D	0.662	neutral	D	0.562426487	None	None	N
V/E	0.8299	likely_pathogenic	0.8734	pathogenic	-2.306	Highly Destabilizing	0.726	D	0.614	neutral	None	None	None	None	N
V/F	0.2443	likely_benign	0.2994	benign	-1.322	Destabilizing	0.331	N	0.581	neutral	D	0.529572112	None	None	N
V/G	0.5871	likely_pathogenic	0.6324	pathogenic	-2.474	Highly Destabilizing	0.667	D	0.653	neutral	D	0.550398619	None	None	N
V/H	0.8684	likely_pathogenic	0.8973	pathogenic	-2.181	Highly Destabilizing	0.968	D	0.624	neutral	None	None	None	None	N
V/I	0.0735	likely_benign	0.0728	benign	-0.802	Destabilizing	0.001	N	0.299	neutral	N	0.494574462	None	None	N
V/K	0.7486	likely_pathogenic	0.7969	pathogenic	-1.861	Destabilizing	0.726	D	0.607	neutral	None	None	None	None	N
V/L	0.1721	likely_benign	0.1879	benign	-0.802	Destabilizing	None	N	0.224	neutral	N	0.508932962	None	None	N
V/M	0.2209	likely_benign	0.2399	benign	-0.603	Destabilizing	0.396	N	0.507	neutral	None	None	None	None	N
V/N	0.8014	likely_pathogenic	0.8416	pathogenic	-1.889	Destabilizing	0.89	D	0.665	neutral	None	None	None	None	N
V/P	0.9574	likely_pathogenic	0.9643	pathogenic	-1.179	Destabilizing	0.89	D	0.61	neutral	None	None	None	None	N
V/Q	0.7306	likely_pathogenic	0.7819	pathogenic	-1.888	Destabilizing	0.89	D	0.617	neutral	None	None	None	None	N
V/R	0.663	likely_pathogenic	0.7217	pathogenic	-1.454	Destabilizing	0.726	D	0.669	neutral	None	None	None	None	N
V/S	0.632	likely_pathogenic	0.6796	pathogenic	-2.444	Highly Destabilizing	0.726	D	0.601	neutral	None	None	None	None	N
V/T	0.4435	ambiguous	0.4869	ambiguous	-2.201	Highly Destabilizing	0.272	N	0.541	neutral	None	None	None	None	N
V/W	0.8924	likely_pathogenic	0.9237	pathogenic	-1.77	Destabilizing	0.968	D	0.592	neutral	None	None	None	None	N
V/Y	0.703	likely_pathogenic	0.7766	pathogenic	-1.435	Destabilizing	0.726	D	0.566	neutral	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.