TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14312	43159;43160;43161	chr2:178633425;178633424;178633423	chr2:179498152;179498151;179498150
N2AB	12671	38236;38237;38238	chr2:178633425;178633424;178633423	chr2:179498152;179498151;179498150
N2A	11744	35455;35456;35457	chr2:178633425;178633424;178633423	chr2:179498152;179498151;179498150
N2B	5247	15964;15965;15966	chr2:178633425;178633424;178633423	chr2:179498152;179498151;179498150
Novex-1	5372	16339;16340;16341	chr2:178633425;178633424;178633423	chr2:179498152;179498151;179498150
Novex-2	5439	16540;16541;16542	chr2:178633425;178633424;178633423	chr2:179498152;179498151;179498150
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-93
• Domain position: 82
• Structural Position: 174
• Q(SASA): 0.1253
• 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
V/I	rs794729429	-0.683	None	N	0.292	0.041	0.101711395817	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
V/I	rs794729429	-0.683	None	N	0.292	0.041	0.101711395817	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.93349E-04	None	0	0	0	0	0
V/I	rs794729429	-0.683	None	N	0.292	0.041	0.101711395817	gnomAD-4.0.0	1.11575E-05	None	None	None	None	N	None	0	0	None	0	2.23354E-05	None	0	0	1.44119E-05	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	0.6332	likely_pathogenic	0.5547	ambiguous	-2.287	Highly Destabilizing	0.052	N	0.651	neutral	N	0.450547923	None	None	N
V/C	0.878	likely_pathogenic	0.8419	pathogenic	-2.313	Highly Destabilizing	0.935	D	0.804	deleterious	None	None	None	None	N
V/D	0.9832	likely_pathogenic	0.9797	pathogenic	-2.962	Highly Destabilizing	0.741	D	0.853	deleterious	D	0.627975742	None	None	N
V/E	0.9626	likely_pathogenic	0.9548	pathogenic	-2.77	Highly Destabilizing	0.555	D	0.813	deleterious	None	None	None	None	N
V/F	0.4406	ambiguous	0.3772	ambiguous	-1.518	Destabilizing	0.188	N	0.791	deleterious	N	0.480797006	None	None	N
V/G	0.797	likely_pathogenic	0.7526	pathogenic	-2.81	Highly Destabilizing	0.484	N	0.825	deleterious	D	0.627975742	None	None	N
V/H	0.9791	likely_pathogenic	0.9754	pathogenic	-2.462	Highly Destabilizing	0.935	D	0.844	deleterious	None	None	None	None	N
V/I	0.0781	likely_benign	0.0723	benign	-0.833	Destabilizing	None	N	0.292	neutral	N	0.458987865	None	None	N
V/K	0.9675	likely_pathogenic	0.9626	pathogenic	-1.966	Destabilizing	0.555	D	0.804	deleterious	None	None	None	None	N
V/L	0.1991	likely_benign	0.1492	benign	-0.833	Destabilizing	None	N	0.331	neutral	N	0.349879342	None	None	N
V/M	0.2658	likely_benign	0.2164	benign	-1.042	Destabilizing	0.235	N	0.699	prob.neutral	None	None	None	None	N
V/N	0.9444	likely_pathogenic	0.9319	pathogenic	-2.302	Highly Destabilizing	0.791	D	0.848	deleterious	None	None	None	None	N
V/P	0.9858	likely_pathogenic	0.9844	pathogenic	-1.29	Destabilizing	0.791	D	0.832	deleterious	None	None	None	None	N
V/Q	0.9552	likely_pathogenic	0.9455	pathogenic	-2.203	Highly Destabilizing	0.791	D	0.821	deleterious	None	None	None	None	N
V/R	0.953	likely_pathogenic	0.9459	pathogenic	-1.698	Destabilizing	0.555	D	0.85	deleterious	None	None	None	None	N
V/S	0.8798	likely_pathogenic	0.8444	pathogenic	-2.958	Highly Destabilizing	0.555	D	0.8	deleterious	None	None	None	None	N
V/T	0.7245	likely_pathogenic	0.6555	pathogenic	-2.616	Highly Destabilizing	0.149	N	0.661	neutral	None	None	None	None	N
V/W	0.9747	likely_pathogenic	0.9641	pathogenic	-1.957	Destabilizing	0.935	D	0.846	deleterious	None	None	None	None	N
V/Y	0.9094	likely_pathogenic	0.8808	pathogenic	-1.625	Destabilizing	0.555	D	0.806	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.