TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32179	96760;96761;96762	chr2:178543438;178543437;178543436	chr2:179408165;179408164;179408163
N2AB	30538	91837;91838;91839	chr2:178543438;178543437;178543436	chr2:179408165;179408164;179408163
N2A	29611	89056;89057;89058	chr2:178543438;178543437;178543436	chr2:179408165;179408164;179408163
N2B	23114	69565;69566;69567	chr2:178543438;178543437;178543436	chr2:179408165;179408164;179408163
Novex-1	23239	69940;69941;69942	chr2:178543438;178543437;178543436	chr2:179408165;179408164;179408163
Novex-2	23306	70141;70142;70143	chr2:178543438;178543437;178543436	chr2:179408165;179408164;179408163
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-122
• Domain position: 75
• Structural Position: 108
• Q(SASA): 0.0887
• 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/M	rs727505082	-1.519	1.0	D	0.763	0.728	0.747598145101	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
V/M	rs727505082	-1.519	1.0	D	0.763	0.728	0.747598145101	gnomAD-4.0.0	1.02636E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.34922E-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	0.9324	likely_pathogenic	0.9182	pathogenic	-2.552	Highly Destabilizing	1.0	D	0.623	neutral	D	0.551821105	None	None	N
V/C	0.9682	likely_pathogenic	0.9654	pathogenic	-1.953	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
V/D	0.9991	likely_pathogenic	0.9988	pathogenic	-3.451	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/E	0.997	likely_pathogenic	0.9958	pathogenic	-3.154	Highly Destabilizing	1.0	D	0.873	deleterious	D	0.623447385	None	None	N
V/F	0.921	likely_pathogenic	0.8774	pathogenic	-1.403	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
V/G	0.9696	likely_pathogenic	0.9573	pathogenic	-3.102	Highly Destabilizing	1.0	D	0.875	deleterious	D	0.623447385	None	None	N
V/H	0.9989	likely_pathogenic	0.9982	pathogenic	-2.89	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/I	0.0929	likely_benign	0.0908	benign	-0.933	Destabilizing	0.999	D	0.595	neutral	None	None	None	None	N
V/K	0.9976	likely_pathogenic	0.9965	pathogenic	-2.082	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
V/L	0.6911	likely_pathogenic	0.6309	pathogenic	-0.933	Destabilizing	0.995	D	0.635	neutral	D	0.536408967	None	None	N
V/M	0.8354	likely_pathogenic	0.7894	pathogenic	-1.22	Destabilizing	1.0	D	0.763	deleterious	D	0.545491229	None	None	N
V/N	0.9952	likely_pathogenic	0.9937	pathogenic	-2.705	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
V/P	0.9966	likely_pathogenic	0.9953	pathogenic	-1.459	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
V/Q	0.9964	likely_pathogenic	0.995	pathogenic	-2.387	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
V/R	0.9952	likely_pathogenic	0.9931	pathogenic	-2.08	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
V/S	0.9833	likely_pathogenic	0.9784	pathogenic	-3.172	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/T	0.955	likely_pathogenic	0.9493	pathogenic	-2.74	Highly Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
V/W	0.9992	likely_pathogenic	0.9985	pathogenic	-1.947	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/Y	0.9943	likely_pathogenic	0.9908	pathogenic	-1.711	Destabilizing	1.0	D	0.81	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.