TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32137	96634;96635;96636	chr2:178543564;178543563;178543562	chr2:179408291;179408290;179408289
N2AB	30496	91711;91712;91713	chr2:178543564;178543563;178543562	chr2:179408291;179408290;179408289
N2A	29569	88930;88931;88932	chr2:178543564;178543563;178543562	chr2:179408291;179408290;179408289
N2B	23072	69439;69440;69441	chr2:178543564;178543563;178543562	chr2:179408291;179408290;179408289
Novex-1	23197	69814;69815;69816	chr2:178543564;178543563;178543562	chr2:179408291;179408290;179408289
Novex-2	23264	70015;70016;70017	chr2:178543564;178543563;178543562	chr2:179408291;179408290;179408289
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: Fn3-122
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.3577
• 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	0.992	N	0.662	0.421	0.54963036629	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-05	0
V/I	rs2857279	None	0.619	N	0.351	0.166	0.352476196916	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/I	rs2857279	None	0.619	N	0.351	0.166	0.352476196916	gnomAD-4.0.0	6.57013E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.46981E-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	0.8681	likely_pathogenic	0.8765	pathogenic	-2.055	Highly Destabilizing	0.992	D	0.662	neutral	N	0.485019722	None	None	I
V/C	0.9478	likely_pathogenic	0.956	pathogenic	-1.343	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
V/D	0.9966	likely_pathogenic	0.9974	pathogenic	-2.848	Highly Destabilizing	1.0	D	0.897	deleterious	N	0.5107573	None	None	I
V/E	0.9891	likely_pathogenic	0.9898	pathogenic	-2.732	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	I
V/F	0.9252	likely_pathogenic	0.9282	pathogenic	-1.417	Destabilizing	0.999	D	0.874	deleterious	N	0.509489852	None	None	I
V/G	0.9471	likely_pathogenic	0.9533	pathogenic	-2.483	Highly Destabilizing	1.0	D	0.882	deleterious	N	0.512531726	None	None	I
V/H	0.9966	likely_pathogenic	0.9972	pathogenic	-2.372	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
V/I	0.0859	likely_benign	0.0902	benign	-0.893	Destabilizing	0.619	D	0.351	neutral	N	0.403574428	None	None	I
V/K	0.9932	likely_pathogenic	0.993	pathogenic	-1.889	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	I
V/L	0.631	likely_pathogenic	0.6727	pathogenic	-0.893	Destabilizing	0.962	D	0.607	neutral	N	0.505493649	None	None	I
V/M	0.6856	likely_pathogenic	0.7179	pathogenic	-0.596	Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	I
V/N	0.9737	likely_pathogenic	0.9859	pathogenic	-1.912	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	I
V/P	0.9338	likely_pathogenic	0.9456	pathogenic	-1.253	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	I
V/Q	0.988	likely_pathogenic	0.9889	pathogenic	-1.917	Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	I
V/R	0.9888	likely_pathogenic	0.9878	pathogenic	-1.497	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	I
V/S	0.9464	likely_pathogenic	0.9577	pathogenic	-2.358	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	I
V/T	0.8705	likely_pathogenic	0.8927	pathogenic	-2.138	Highly Destabilizing	0.997	D	0.813	deleterious	None	None	None	None	I
V/W	0.9983	likely_pathogenic	0.9983	pathogenic	-1.955	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	I
V/Y	0.9924	likely_pathogenic	0.9926	pathogenic	-1.634	Destabilizing	1.0	D	0.874	deleterious	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.