TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18076	54451;54452;54453	chr2:178604863;178604862;178604861	chr2:179469590;179469589;179469588
N2AB	16435	49528;49529;49530	chr2:178604863;178604862;178604861	chr2:179469590;179469589;179469588
N2A	15508	46747;46748;46749	chr2:178604863;178604862;178604861	chr2:179469590;179469589;179469588
N2B	9011	27256;27257;27258	chr2:178604863;178604862;178604861	chr2:179469590;179469589;179469588
Novex-1	9136	27631;27632;27633	chr2:178604863;178604862;178604861	chr2:179469590;179469589;179469588
Novex-2	9203	27832;27833;27834	chr2:178604863;178604862;178604861	chr2:179469590;179469589;179469588
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-19
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.4418
• 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
D/N	rs1250676624	None	0.122	N	0.115	0.199	0.17948927462	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
D/N	rs1250676624	None	0.122	N	0.115	0.199	0.17948927462	gnomAD-4.0.0	2.03057E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.4102E-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
D/A	0.5223	ambiguous	0.4823	ambiguous	-0.556	Destabilizing	0.925	D	0.514	neutral	D	0.523463334	None	None	N
D/C	0.9249	likely_pathogenic	0.9142	pathogenic	-0.23	Destabilizing	1.0	D	0.66	neutral	None	None	None	None	N
D/E	0.4394	ambiguous	0.3709	ambiguous	-0.387	Destabilizing	0.91	D	0.476	neutral	N	0.463164237	None	None	N
D/F	0.9406	likely_pathogenic	0.9315	pathogenic	-0.178	Destabilizing	0.999	D	0.658	neutral	None	None	None	None	N
D/G	0.4444	ambiguous	0.3917	ambiguous	-0.817	Destabilizing	0.91	D	0.505	neutral	N	0.466773655	None	None	N
D/H	0.7592	likely_pathogenic	0.7228	pathogenic	-0.116	Destabilizing	0.994	D	0.587	neutral	N	0.47390368	None	None	N
D/I	0.9179	likely_pathogenic	0.909	pathogenic	0.109	Stabilizing	0.996	D	0.65	neutral	None	None	None	None	N
D/K	0.8804	likely_pathogenic	0.8565	pathogenic	-0.018	Destabilizing	0.97	D	0.521	neutral	None	None	None	None	N
D/L	0.8822	likely_pathogenic	0.8541	pathogenic	0.109	Stabilizing	0.996	D	0.587	neutral	None	None	None	None	N
D/M	0.9383	likely_pathogenic	0.924	pathogenic	0.297	Stabilizing	1.0	D	0.648	neutral	None	None	None	None	N
D/N	0.2002	likely_benign	0.1798	benign	-0.463	Destabilizing	0.122	N	0.115	neutral	N	0.493756503	None	None	N
D/P	0.9784	likely_pathogenic	0.9774	pathogenic	-0.09	Destabilizing	0.996	D	0.569	neutral	None	None	None	None	N
D/Q	0.7867	likely_pathogenic	0.7522	pathogenic	-0.387	Destabilizing	0.996	D	0.496	neutral	None	None	None	None	N
D/R	0.8719	likely_pathogenic	0.8568	pathogenic	0.253	Stabilizing	0.996	D	0.605	neutral	None	None	None	None	N
D/S	0.3655	ambiguous	0.3205	benign	-0.608	Destabilizing	0.559	D	0.253	neutral	None	None	None	None	N
D/T	0.7209	likely_pathogenic	0.6696	pathogenic	-0.396	Destabilizing	0.942	D	0.486	neutral	None	None	None	None	N
D/V	0.7889	likely_pathogenic	0.7704	pathogenic	-0.09	Destabilizing	0.994	D	0.609	neutral	N	0.475927915	None	None	N
D/W	0.9846	likely_pathogenic	0.9829	pathogenic	0.067	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
D/Y	0.6885	likely_pathogenic	0.6691	pathogenic	0.076	Stabilizing	0.998	D	0.659	neutral	N	0.483943312	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.