TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6636	20131;20132;20133	chr2:178727672;178727671;178727670	chr2:179592399;179592398;179592397
N2AB	6319	19180;19181;19182	chr2:178727672;178727671;178727670	chr2:179592399;179592398;179592397
N2A	5392	16399;16400;16401	chr2:178727672;178727671;178727670	chr2:179592399;179592398;179592397
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-50
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.1125
• 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	rs1258812731	-2.191	1.0	D	0.531	0.499	0.729420930906	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	1.1605E-04	None	0	0	None	0	None	0	0	0
V/A	rs1258812731	-2.191	1.0	D	0.531	0.499	0.729420930906	gnomAD-4.0.0	4.77824E-06	None	None	None	None	N	None	0	6.86091E-05	None	0	0	None	0	0	0	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	0.3178	likely_benign	0.3004	benign	-2.013	Highly Destabilizing	1.0	D	0.531	neutral	D	0.527211007	None	None	N
V/C	0.9045	likely_pathogenic	0.8973	pathogenic	-2.248	Highly Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
V/D	0.9517	likely_pathogenic	0.9562	pathogenic	-2.84	Highly Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
V/E	0.9115	likely_pathogenic	0.9189	pathogenic	-2.755	Highly Destabilizing	1.0	D	0.755	deleterious	D	0.561350077	None	None	N
V/F	0.6377	likely_pathogenic	0.6563	pathogenic	-1.565	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
V/G	0.6466	likely_pathogenic	0.6466	pathogenic	-2.4	Highly Destabilizing	1.0	D	0.747	deleterious	D	0.549993772	None	None	N
V/H	0.9769	likely_pathogenic	0.9791	pathogenic	-1.84	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
V/I	0.1105	likely_benign	0.1055	benign	-0.988	Destabilizing	0.966	D	0.5	neutral	None	None	None	None	N
V/K	0.9483	likely_pathogenic	0.9554	pathogenic	-1.767	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
V/L	0.4808	ambiguous	0.4737	ambiguous	-0.988	Destabilizing	0.997	D	0.546	neutral	N	0.498070409	None	None	N
V/M	0.3566	ambiguous	0.3425	ambiguous	-1.135	Destabilizing	1.0	D	0.787	deleterious	D	0.542738843	None	None	N
V/N	0.8801	likely_pathogenic	0.8777	pathogenic	-1.949	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
V/P	0.8216	likely_pathogenic	0.8852	pathogenic	-1.301	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
V/Q	0.9237	likely_pathogenic	0.9279	pathogenic	-2.071	Highly Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
V/R	0.9224	likely_pathogenic	0.9359	pathogenic	-1.285	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
V/S	0.6197	likely_pathogenic	0.6019	pathogenic	-2.508	Highly Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
V/T	0.3535	ambiguous	0.3179	benign	-2.301	Highly Destabilizing	0.999	D	0.631	neutral	None	None	None	None	N
V/W	0.9854	likely_pathogenic	0.9864	pathogenic	-1.831	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
V/Y	0.9601	likely_pathogenic	0.9651	pathogenic	-1.521	Destabilizing	1.0	D	0.787	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.