TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25068	75427;75428;75429	chr2:178570930;178570929;178570928	chr2:179435657;179435656;179435655
N2AB	23427	70504;70505;70506	chr2:178570930;178570929;178570928	chr2:179435657;179435656;179435655
N2A	22500	67723;67724;67725	chr2:178570930;178570929;178570928	chr2:179435657;179435656;179435655
N2B	16003	48232;48233;48234	chr2:178570930;178570929;178570928	chr2:179435657;179435656;179435655
Novex-1	16128	48607;48608;48609	chr2:178570930;178570929;178570928	chr2:179435657;179435656;179435655
Novex-2	16195	48808;48809;48810	chr2:178570930;178570929;178570928	chr2:179435657;179435656;179435655
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-70
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.1295
• 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	0.553	0.236	0.546824882953	gnomAD-4.0.0	1.59169E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85935E-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	0.5417	ambiguous	0.5426	ambiguous	-1.594	Destabilizing	0.999	D	0.642	neutral	D	0.523700981	None	None	N
V/C	0.9269	likely_pathogenic	0.9316	pathogenic	-1.304	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
V/D	0.9876	likely_pathogenic	0.986	pathogenic	-1.859	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
V/E	0.9655	likely_pathogenic	0.9637	pathogenic	-1.586	Destabilizing	1.0	D	0.827	deleterious	D	0.529945327	None	None	N
V/F	0.794	likely_pathogenic	0.7778	pathogenic	-0.873	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
V/G	0.8467	likely_pathogenic	0.8342	pathogenic	-2.184	Highly Destabilizing	1.0	D	0.835	deleterious	D	0.548049582	None	None	N
V/H	0.9912	likely_pathogenic	0.991	pathogenic	-2.072	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
V/I	0.1155	likely_benign	0.1082	benign	0.064	Stabilizing	0.997	D	0.553	neutral	N	0.485217164	None	None	N
V/K	0.9837	likely_pathogenic	0.9818	pathogenic	-1.17	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
V/L	0.654	likely_pathogenic	0.6483	pathogenic	0.064	Stabilizing	0.997	D	0.658	neutral	N	0.465061681	None	None	N
V/M	0.5519	ambiguous	0.5375	ambiguous	-0.214	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
V/N	0.9597	likely_pathogenic	0.9552	pathogenic	-1.628	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
V/P	0.988	likely_pathogenic	0.988	pathogenic	-0.461	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
V/Q	0.9726	likely_pathogenic	0.9711	pathogenic	-1.32	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/R	0.9794	likely_pathogenic	0.9772	pathogenic	-1.341	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/S	0.8835	likely_pathogenic	0.8755	pathogenic	-2.31	Highly Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
V/T	0.7522	likely_pathogenic	0.748	pathogenic	-1.858	Destabilizing	0.999	D	0.607	neutral	None	None	None	None	N
V/W	0.9959	likely_pathogenic	0.9958	pathogenic	-1.366	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
V/Y	0.9705	likely_pathogenic	0.9685	pathogenic	-0.904	Destabilizing	1.0	D	0.785	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.