TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9998	30217;30218;30219	chr2:178704378;178704377;178704376	chr2:179569105;179569104;179569103
N2AB	9681	29266;29267;29268	chr2:178704378;178704377;178704376	chr2:179569105;179569104;179569103
N2A	8754	26485;26486;26487	chr2:178704378;178704377;178704376	chr2:179569105;179569104;179569103
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-85
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.2093
• 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/M	rs1359452427	-0.558	0.989	None	0.493	0.371	0.622397550212	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.86E-06	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	0.2788	likely_benign	0.2715	benign	-1.355	Destabilizing	0.267	N	0.32	neutral	None	None	None	None	N
V/C	0.8693	likely_pathogenic	0.8897	pathogenic	-0.732	Destabilizing	0.998	D	0.467	neutral	None	None	None	None	N
V/D	0.5305	ambiguous	0.4811	ambiguous	-1.444	Destabilizing	0.842	D	0.517	neutral	None	None	None	None	N
V/E	0.4023	ambiguous	0.3521	ambiguous	-1.492	Destabilizing	0.801	D	0.476	neutral	None	None	None	None	N
V/F	0.2566	likely_benign	0.2506	benign	-1.206	Destabilizing	0.974	D	0.495	neutral	None	None	None	None	N
V/G	0.4083	ambiguous	0.4185	ambiguous	-1.623	Destabilizing	0.669	D	0.497	neutral	None	None	None	None	N
V/H	0.7146	likely_pathogenic	0.7082	pathogenic	-1.294	Destabilizing	0.998	D	0.525	neutral	None	None	None	None	N
V/I	0.088	likely_benign	0.0871	benign	-0.733	Destabilizing	0.688	D	0.473	neutral	None	None	None	None	N
V/K	0.4336	ambiguous	0.386	ambiguous	-1.252	Destabilizing	0.067	N	0.333	neutral	None	None	None	None	N
V/L	0.3268	likely_benign	0.3127	benign	-0.733	Destabilizing	0.454	N	0.403	neutral	None	None	None	None	N
V/M	0.1655	likely_benign	0.1616	benign	-0.43	Destabilizing	0.989	D	0.493	neutral	None	None	None	None	N
V/N	0.3998	ambiguous	0.3854	ambiguous	-0.902	Destabilizing	0.842	D	0.513	neutral	None	None	None	None	N
V/P	0.9687	likely_pathogenic	0.9735	pathogenic	-0.906	Destabilizing	0.974	D	0.505	neutral	None	None	None	None	N
V/Q	0.4293	ambiguous	0.4075	ambiguous	-1.137	Destabilizing	0.949	D	0.499	neutral	None	None	None	None	N
V/R	0.4126	ambiguous	0.3826	ambiguous	-0.661	Destabilizing	0.728	D	0.522	neutral	None	None	None	None	N
V/S	0.3574	ambiguous	0.3571	ambiguous	-1.288	Destabilizing	0.067	N	0.338	neutral	None	None	None	None	N
V/T	0.2148	likely_benign	0.2083	benign	-1.243	Destabilizing	0.01	N	0.114	neutral	None	None	None	None	N
V/W	0.9183	likely_pathogenic	0.9205	pathogenic	-1.39	Destabilizing	0.998	D	0.555	neutral	None	None	None	None	N
V/Y	0.7176	likely_pathogenic	0.7173	pathogenic	-1.127	Destabilizing	0.991	D	0.508	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.