TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7273	22042;22043;22044	chr2:178723190;178723189;178723188	chr2:179587917;179587916;179587915
N2AB	6956	21091;21092;21093	chr2:178723190;178723189;178723188	chr2:179587917;179587916;179587915
N2A	6029	18310;18311;18312	chr2:178723190;178723189;178723188	chr2:179587917;179587916;179587915
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-57
• Domain position: 44
• Structural Position: 73
• Q(SASA): 0.2674
• 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
S/F	rs768091794	-0.981	0.999	N	0.693	0.342	0.606518698375	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
S/F	rs768091794	-0.981	0.999	N	0.693	0.342	0.606518698375	gnomAD-4.0.0	6.36791E-06	None	None	None	None	N	None	0	0	None	0	1.10994E-04	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
S/A	0.1356	likely_benign	0.1247	benign	-0.221	Destabilizing	0.992	D	0.368	neutral	N	0.477687617	None	None	N
S/C	0.2637	likely_benign	0.2173	benign	-0.171	Destabilizing	1.0	D	0.625	neutral	D	0.526039355	None	None	N
S/D	0.494	ambiguous	0.4382	ambiguous	0.036	Stabilizing	0.997	D	0.447	neutral	None	None	None	None	N
S/E	0.7513	likely_pathogenic	0.6903	pathogenic	-0.076	Destabilizing	0.997	D	0.445	neutral	None	None	None	None	N
S/F	0.4606	ambiguous	0.3997	ambiguous	-0.933	Destabilizing	0.999	D	0.693	prob.neutral	N	0.50768161	None	None	N
S/G	0.1126	likely_benign	0.1144	benign	-0.286	Destabilizing	0.994	D	0.456	neutral	None	None	None	None	N
S/H	0.6538	likely_pathogenic	0.5653	pathogenic	-0.799	Destabilizing	1.0	D	0.623	neutral	None	None	None	None	N
S/I	0.5463	ambiguous	0.4455	ambiguous	-0.181	Destabilizing	0.999	D	0.682	prob.neutral	None	None	None	None	N
S/K	0.8883	likely_pathogenic	0.8384	pathogenic	-0.375	Destabilizing	0.997	D	0.446	neutral	None	None	None	None	N
S/L	0.1922	likely_benign	0.1616	benign	-0.181	Destabilizing	0.997	D	0.557	neutral	None	None	None	None	N
S/M	0.3932	ambiguous	0.344	ambiguous	0.069	Stabilizing	1.0	D	0.623	neutral	None	None	None	None	N
S/N	0.2734	likely_benign	0.2404	benign	-0.064	Destabilizing	0.997	D	0.449	neutral	None	None	None	None	N
S/P	0.7413	likely_pathogenic	0.6081	pathogenic	-0.169	Destabilizing	0.999	D	0.61	neutral	N	0.488981471	None	None	N
S/Q	0.7973	likely_pathogenic	0.7414	pathogenic	-0.337	Destabilizing	0.999	D	0.601	neutral	None	None	None	None	N
S/R	0.8476	likely_pathogenic	0.7892	pathogenic	-0.165	Destabilizing	0.999	D	0.616	neutral	None	None	None	None	N
S/T	0.1053	likely_benign	0.0966	benign	-0.17	Destabilizing	0.992	D	0.451	neutral	N	0.469356278	None	None	N
S/V	0.4499	ambiguous	0.3744	ambiguous	-0.169	Destabilizing	0.999	D	0.605	neutral	None	None	None	None	N
S/W	0.6027	likely_pathogenic	0.5262	ambiguous	-0.986	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
S/Y	0.4249	ambiguous	0.3567	ambiguous	-0.682	Destabilizing	0.999	D	0.69	prob.neutral	N	0.496325305	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.