TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35203	105832;105833;105834	chr2:178531008;178531007;178531006	chr2:179395735;179395734;179395733
N2AB	33562	100909;100910;100911	chr2:178531008;178531007;178531006	chr2:179395735;179395734;179395733
N2A	32635	98128;98129;98130	chr2:178531008;178531007;178531006	chr2:179395735;179395734;179395733
N2B	26138	78637;78638;78639	chr2:178531008;178531007;178531006	chr2:179395735;179395734;179395733
Novex-1	26263	79012;79013;79014	chr2:178531008;178531007;178531006	chr2:179395735;179395734;179395733
Novex-2	26330	79213;79214;79215	chr2:178531008;178531007;178531006	chr2:179395735;179395734;179395733
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: Ig-164
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.093
• 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	rs771136390	-2.418	0.316	N	0.323	0.274	None	gnomAD-2.1.1	4.28E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.35E-05	0
V/A	rs771136390	-2.418	0.316	N	0.323	0.274	None	gnomAD-3.1.2	4.61E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.02965E-04	0	0
V/A	rs771136390	-2.418	0.316	N	0.323	0.274	None	gnomAD-4.0.0	6.50725E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.13664E-05	0	1.44088E-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	0.4248	ambiguous	0.4509	ambiguous	-2.279	Highly Destabilizing	0.316	N	0.323	neutral	N	0.454915687	None	None	N
V/C	0.9572	likely_pathogenic	0.9459	pathogenic	-2.193	Highly Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
V/D	0.9953	likely_pathogenic	0.9965	pathogenic	-3.406	Highly Destabilizing	0.997	D	0.865	deleterious	None	None	None	None	N
V/E	0.9804	likely_pathogenic	0.9856	pathogenic	-3.247	Highly Destabilizing	0.996	D	0.837	deleterious	D	0.549562471	None	None	N
V/F	0.8791	likely_pathogenic	0.8824	pathogenic	-1.143	Destabilizing	0.999	D	0.842	deleterious	None	None	None	None	N
V/G	0.8159	likely_pathogenic	0.8455	pathogenic	-2.685	Highly Destabilizing	0.992	D	0.795	deleterious	N	0.508327532	None	None	N
V/H	0.997	likely_pathogenic	0.9976	pathogenic	-2.077	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
V/I	0.1533	likely_benign	0.1436	benign	-1.15	Destabilizing	0.966	D	0.559	neutral	N	0.500196776	None	None	N
V/K	0.9909	likely_pathogenic	0.9934	pathogenic	-1.89	Destabilizing	0.997	D	0.844	deleterious	None	None	None	None	N
V/L	0.6941	likely_pathogenic	0.6668	pathogenic	-1.15	Destabilizing	0.934	D	0.631	neutral	N	0.491918344	None	None	N
V/M	0.6636	likely_pathogenic	0.6624	pathogenic	-1.509	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
V/N	0.99	likely_pathogenic	0.991	pathogenic	-2.226	Highly Destabilizing	0.999	D	0.874	deleterious	None	None	None	None	N
V/P	0.9936	likely_pathogenic	0.9958	pathogenic	-1.505	Destabilizing	0.997	D	0.854	deleterious	None	None	None	None	N
V/Q	0.9795	likely_pathogenic	0.9841	pathogenic	-2.171	Highly Destabilizing	0.999	D	0.864	deleterious	None	None	None	None	N
V/R	0.9781	likely_pathogenic	0.9839	pathogenic	-1.552	Destabilizing	0.997	D	0.87	deleterious	None	None	None	None	N
V/S	0.8526	likely_pathogenic	0.8654	pathogenic	-2.659	Highly Destabilizing	0.988	D	0.799	deleterious	None	None	None	None	N
V/T	0.6308	likely_pathogenic	0.6347	pathogenic	-2.396	Highly Destabilizing	0.979	D	0.651	neutral	None	None	None	None	N
V/W	0.9971	likely_pathogenic	0.9975	pathogenic	-1.549	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
V/Y	0.991	likely_pathogenic	0.9922	pathogenic	-1.35	Destabilizing	0.999	D	0.841	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.