TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14121	42586;42587;42588	chr2:178634420;178634419;178634418	chr2:179499147;179499146;179499145
N2AB	12480	37663;37664;37665	chr2:178634420;178634419;178634418	chr2:179499147;179499146;179499145
N2A	11553	34882;34883;34884	chr2:178634420;178634419;178634418	chr2:179499147;179499146;179499145
N2B	5056	15391;15392;15393	chr2:178634420;178634419;178634418	chr2:179499147;179499146;179499145
Novex-1	5181	15766;15767;15768	chr2:178634420;178634419;178634418	chr2:179499147;179499146;179499145
Novex-2	5248	15967;15968;15969	chr2:178634420;178634419;178634418	chr2:179499147;179499146;179499145
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-91
• Domain position: 68
• Structural Position: 153
• Q(SASA): 0.422
• Predicted PPI site: I

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	0.244	N	0.281	0.186	0.601974941769	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
V/F	None	None	0.006	N	0.249	0.244	0.776660857837	gnomAD-4.0.0	6.3716E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.58192E-06	1.43332E-05	0
V/G	None	None	0.425	D	0.406	0.319	0.827173928948	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1602	likely_benign	0.1657	benign	-1.265	Destabilizing	0.244	N	0.281	neutral	N	0.508927476	None	None	I
V/C	0.6968	likely_pathogenic	0.6636	pathogenic	-0.98	Destabilizing	0.995	D	0.458	neutral	None	None	None	None	I
V/D	0.1517	likely_benign	0.1448	benign	-0.427	Destabilizing	0.002	N	0.392	neutral	N	0.477807057	None	None	I
V/E	0.1175	likely_benign	0.1325	benign	-0.428	Destabilizing	0.001	N	0.27	neutral	None	None	None	None	I
V/F	0.1504	likely_benign	0.1231	benign	-0.992	Destabilizing	0.006	N	0.249	neutral	N	0.506025056	None	None	I
V/G	0.2279	likely_benign	0.2364	benign	-1.567	Destabilizing	0.425	N	0.406	neutral	D	0.549872353	None	None	I
V/H	0.4453	ambiguous	0.4558	ambiguous	-0.996	Destabilizing	0.944	D	0.519	neutral	None	None	None	None	I
V/I	0.0652	likely_benign	0.0661	benign	-0.55	Destabilizing	0.27	N	0.405	neutral	N	0.481875953	None	None	I
V/K	0.262	likely_benign	0.2773	benign	-0.77	Destabilizing	0.329	N	0.353	neutral	None	None	None	None	I
V/L	0.1306	likely_benign	0.1267	benign	-0.55	Destabilizing	0.27	N	0.328	neutral	N	0.494708491	None	None	I
V/M	0.1099	likely_benign	0.1135	benign	-0.524	Destabilizing	0.944	D	0.468	neutral	None	None	None	None	I
V/N	0.1334	likely_benign	0.1317	benign	-0.577	Destabilizing	0.704	D	0.459	neutral	None	None	None	None	I
V/P	0.5515	ambiguous	0.5041	ambiguous	-0.752	Destabilizing	0.828	D	0.493	neutral	None	None	None	None	I
V/Q	0.2088	likely_benign	0.2357	benign	-0.723	Destabilizing	0.085	N	0.325	neutral	None	None	None	None	I
V/R	0.2857	likely_benign	0.295	benign	-0.354	Destabilizing	0.704	D	0.484	neutral	None	None	None	None	I
V/S	0.1564	likely_benign	0.1603	benign	-1.23	Destabilizing	0.495	N	0.355	neutral	None	None	None	None	I
V/T	0.119	likely_benign	0.1301	benign	-1.109	Destabilizing	0.495	N	0.386	neutral	None	None	None	None	I
V/W	0.7405	likely_pathogenic	0.7279	pathogenic	-1.097	Destabilizing	0.995	D	0.501	neutral	None	None	None	None	I
V/Y	0.4347	ambiguous	0.4045	ambiguous	-0.788	Destabilizing	0.543	D	0.491	neutral	None	None	None	None	I

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.