TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9462	28609;28610;28611	chr2:178710713;178710712;178710711	chr2:179575440;179575439;179575438
N2AB	9145	27658;27659;27660	chr2:178710713;178710712;178710711	chr2:179575440;179575439;179575438
N2A	8218	24877;24878;24879	chr2:178710713;178710712;178710711	chr2:179575440;179575439;179575438
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: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-80
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.3385
• 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/E	rs866946485	-0.202	0.968	None	0.523	0.271	0.231231049324	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
G/V	None	None	0.938	None	0.559	0.248	0.344483371355	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
G/V	None	None	0.938	None	0.559	0.248	0.344483371355	gnomAD-4.0.0	6.57272E-06	None	None	None	None	N	None	2.41418E-05	0	None	0	0	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	0.1047	likely_benign	0.1194	benign	-0.2	Destabilizing	0.103	N	0.168	neutral	None	None	None	None	N
G/C	0.3842	ambiguous	0.4041	ambiguous	-0.85	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
G/D	0.2503	likely_benign	0.2407	benign	-0.372	Destabilizing	0.976	D	0.468	neutral	None	None	None	None	N
G/E	0.225	likely_benign	0.1992	benign	-0.533	Destabilizing	0.968	D	0.523	neutral	None	None	None	None	N
G/F	0.6003	likely_pathogenic	0.6353	pathogenic	-0.943	Destabilizing	0.976	D	0.649	neutral	None	None	None	None	N
G/H	0.4448	ambiguous	0.522	ambiguous	-0.372	Destabilizing	0.999	D	0.599	neutral	None	None	None	None	N
G/I	0.2737	likely_benign	0.3325	benign	-0.375	Destabilizing	0.952	D	0.636	neutral	None	None	None	None	N
G/K	0.4383	ambiguous	0.5029	ambiguous	-0.636	Destabilizing	0.976	D	0.52	neutral	None	None	None	None	N
G/L	0.3943	ambiguous	0.4713	ambiguous	-0.375	Destabilizing	0.076	N	0.426	neutral	None	None	None	None	N
G/M	0.3918	ambiguous	0.4905	ambiguous	-0.428	Destabilizing	0.993	D	0.641	neutral	None	None	None	None	N
G/N	0.2313	likely_benign	0.2733	benign	-0.323	Destabilizing	0.976	D	0.488	neutral	None	None	None	None	N
G/P	0.7822	likely_pathogenic	0.8566	pathogenic	-0.286	Destabilizing	0.988	D	0.601	neutral	None	None	None	None	N
G/Q	0.3282	likely_benign	0.3755	ambiguous	-0.589	Destabilizing	0.988	D	0.606	neutral	None	None	None	None	N
G/R	0.3456	ambiguous	0.3777	ambiguous	-0.216	Destabilizing	0.968	D	0.601	neutral	None	None	None	None	N
G/S	0.0994	likely_benign	0.1026	benign	-0.496	Destabilizing	0.132	N	0.243	neutral	None	None	None	None	N
G/T	0.1303	likely_benign	0.1606	benign	-0.581	Destabilizing	0.851	D	0.511	neutral	None	None	None	None	N
G/V	0.1791	likely_benign	0.2176	benign	-0.286	Destabilizing	0.938	D	0.559	neutral	None	None	None	None	N
G/W	0.4135	ambiguous	0.4784	ambiguous	-1.083	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	N
G/Y	0.4586	ambiguous	0.523	ambiguous	-0.733	Destabilizing	0.996	D	0.646	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.