TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22349	67270;67271;67272	chr2:178580334;178580333;178580332	chr2:179445061;179445060;179445059
N2AB	20708	62347;62348;62349	chr2:178580334;178580333;178580332	chr2:179445061;179445060;179445059
N2A	19781	59566;59567;59568	chr2:178580334;178580333;178580332	chr2:179445061;179445060;179445059
N2B	13284	40075;40076;40077	chr2:178580334;178580333;178580332	chr2:179445061;179445060;179445059
Novex-1	13409	40450;40451;40452	chr2:178580334;178580333;178580332	chr2:179445061;179445060;179445059
Novex-2	13476	40651;40652;40653	chr2:178580334;178580333;178580332	chr2:179445061;179445060;179445059
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-126
• Domain position: 85
• Structural Position: 174
• Q(SASA): 0.1311
• 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	None	None	0.999	N	0.628	0.448	0.657750020267	gnomAD-4.0.0	1.59393E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86139E-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	0.9377	likely_pathogenic	0.9321	pathogenic	-2.209	Highly Destabilizing	0.999	D	0.628	neutral	N	0.516039402	None	None	N
V/C	0.9663	likely_pathogenic	0.9579	pathogenic	-1.713	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
V/D	0.9991	likely_pathogenic	0.9991	pathogenic	-2.959	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/E	0.9969	likely_pathogenic	0.9969	pathogenic	-2.71	Highly Destabilizing	1.0	D	0.856	deleterious	N	0.516546381	None	None	N
V/F	0.9233	likely_pathogenic	0.9327	pathogenic	-1.318	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
V/G	0.9625	likely_pathogenic	0.9627	pathogenic	-2.781	Highly Destabilizing	1.0	D	0.853	deleterious	N	0.516546381	None	None	N
V/H	0.9991	likely_pathogenic	0.9992	pathogenic	-2.59	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
V/I	0.1465	likely_benign	0.1356	benign	-0.594	Destabilizing	0.998	D	0.544	neutral	None	None	None	None	N
V/K	0.9967	likely_pathogenic	0.9973	pathogenic	-2.008	Highly Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
V/L	0.7484	likely_pathogenic	0.7421	pathogenic	-0.594	Destabilizing	0.997	D	0.647	neutral	N	0.439349745	None	None	N
V/M	0.8635	likely_pathogenic	0.8554	pathogenic	-0.599	Destabilizing	1.0	D	0.774	deleterious	N	0.515532423	None	None	N
V/N	0.9956	likely_pathogenic	0.9953	pathogenic	-2.421	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/P	0.9955	likely_pathogenic	0.9959	pathogenic	-1.107	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/Q	0.9961	likely_pathogenic	0.9964	pathogenic	-2.208	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/R	0.9941	likely_pathogenic	0.9954	pathogenic	-1.852	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
V/S	0.9849	likely_pathogenic	0.9842	pathogenic	-3.025	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/T	0.9366	likely_pathogenic	0.9264	pathogenic	-2.626	Highly Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
V/W	0.9992	likely_pathogenic	0.9993	pathogenic	-1.911	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
V/Y	0.9956	likely_pathogenic	0.9964	pathogenic	-1.511	Destabilizing	1.0	D	0.816	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.