TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23426	70501;70502;70503	chr2:178575856;178575855;178575854	chr2:179440583;179440582;179440581
N2AB	21785	65578;65579;65580	chr2:178575856;178575855;178575854	chr2:179440583;179440582;179440581
N2A	20858	62797;62798;62799	chr2:178575856;178575855;178575854	chr2:179440583;179440582;179440581
N2B	14361	43306;43307;43308	chr2:178575856;178575855;178575854	chr2:179440583;179440582;179440581
Novex-1	14486	43681;43682;43683	chr2:178575856;178575855;178575854	chr2:179440583;179440582;179440581
Novex-2	14553	43882;43883;43884	chr2:178575856;178575855;178575854	chr2:179440583;179440582;179440581
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-129
• Domain position: 82
• Structural Position: 169
• Q(SASA): 0.2716
• 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
G/A	None	None	0.983	N	0.583	0.322	0.197625483188	gnomAD-4.0.0	1.59168E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43299E-05	0
G/V	None	None	0.652	N	0.645	0.381	0.594056560588	gnomAD-4.0.0	1.59168E-06	None	None	None	None	N	None	0	0	None	0	2.77454E-05	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
G/A	0.1782	likely_benign	0.166	benign	-0.297	Destabilizing	0.983	D	0.583	neutral	N	0.422000766	None	None	N
G/C	0.4245	ambiguous	0.3971	ambiguous	-0.623	Destabilizing	1.0	D	0.809	deleterious	N	0.498213465	None	None	N
G/D	0.9407	likely_pathogenic	0.9189	pathogenic	-0.128	Destabilizing	1.0	D	0.839	deleterious	N	0.503504641	None	None	N
G/E	0.9437	likely_pathogenic	0.9221	pathogenic	-0.171	Destabilizing	0.999	D	0.854	deleterious	None	None	None	None	N
G/F	0.9269	likely_pathogenic	0.9192	pathogenic	-0.601	Destabilizing	0.999	D	0.85	deleterious	None	None	None	None	N
G/H	0.947	likely_pathogenic	0.9294	pathogenic	-0.791	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
G/I	0.7071	likely_pathogenic	0.6505	pathogenic	0.074	Stabilizing	0.996	D	0.837	deleterious	None	None	None	None	N
G/K	0.9741	likely_pathogenic	0.9672	pathogenic	-0.692	Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
G/L	0.8428	likely_pathogenic	0.8172	pathogenic	0.074	Stabilizing	0.996	D	0.824	deleterious	None	None	None	None	N
G/M	0.8681	likely_pathogenic	0.8424	pathogenic	-0.152	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
G/N	0.897	likely_pathogenic	0.8608	pathogenic	-0.39	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
G/P	0.9951	likely_pathogenic	0.9942	pathogenic	-0.007	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
G/Q	0.9258	likely_pathogenic	0.9037	pathogenic	-0.468	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
G/R	0.9277	likely_pathogenic	0.9141	pathogenic	-0.529	Destabilizing	0.999	D	0.859	deleterious	N	0.517241943	None	None	N
G/S	0.2904	likely_benign	0.2355	benign	-0.731	Destabilizing	0.999	D	0.751	deleterious	N	0.470429431	None	None	N
G/T	0.4872	ambiguous	0.4562	ambiguous	-0.662	Destabilizing	0.998	D	0.845	deleterious	None	None	None	None	N
G/V	0.5437	ambiguous	0.5011	ambiguous	-0.007	Destabilizing	0.652	D	0.645	neutral	N	0.45540405	None	None	N
G/W	0.9257	likely_pathogenic	0.9101	pathogenic	-0.96	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
G/Y	0.9225	likely_pathogenic	0.9004	pathogenic	-0.488	Destabilizing	1.0	D	0.851	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.