TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32114	96565;96566;96567	chr2:178543633;178543632;178543631	chr2:179408360;179408359;179408358
N2AB	30473	91642;91643;91644	chr2:178543633;178543632;178543631	chr2:179408360;179408359;179408358
N2A	29546	88861;88862;88863	chr2:178543633;178543632;178543631	chr2:179408360;179408359;179408358
N2B	23049	69370;69371;69372	chr2:178543633;178543632;178543631	chr2:179408360;179408359;179408358
Novex-1	23174	69745;69746;69747	chr2:178543633;178543632;178543631	chr2:179408360;179408359;179408358
Novex-2	23241	69946;69947;69948	chr2:178543633;178543632;178543631	chr2:179408360;179408359;179408358
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: Fn3-122
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.3018
• 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/L	None	None	0.18	N	0.422	0.175	0.416202232284	gnomAD-4.0.0	1.38198E-06	None	None	None	None	N	None	0	0	None	0	2.53062E-05	None	0	0	9.01733E-07	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	0.4322	ambiguous	0.3777	ambiguous	-1.257	Destabilizing	0.873	D	0.518	neutral	N	0.511574259	None	None	N
V/C	0.8049	likely_pathogenic	0.7734	pathogenic	-0.926	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
V/D	0.9292	likely_pathogenic	0.9215	pathogenic	-1.024	Destabilizing	0.997	D	0.855	deleterious	N	0.514447965	None	None	N
V/E	0.8391	likely_pathogenic	0.8307	pathogenic	-1.009	Destabilizing	0.987	D	0.839	deleterious	None	None	None	None	N
V/F	0.467	ambiguous	0.4189	ambiguous	-0.899	Destabilizing	0.978	D	0.803	deleterious	N	0.470131471	None	None	N
V/G	0.6157	likely_pathogenic	0.565	pathogenic	-1.576	Destabilizing	0.998	D	0.834	deleterious	N	0.495329752	None	None	N
V/H	0.9432	likely_pathogenic	0.9367	pathogenic	-1.029	Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
V/I	0.0871	likely_benign	0.0887	benign	-0.487	Destabilizing	0.003	N	0.231	neutral	N	0.477213756	None	None	N
V/K	0.8923	likely_pathogenic	0.8819	pathogenic	-1.167	Destabilizing	0.982	D	0.841	deleterious	None	None	None	None	N
V/L	0.3844	ambiguous	0.3465	ambiguous	-0.487	Destabilizing	0.18	N	0.422	neutral	N	0.519676454	None	None	N
V/M	0.3221	likely_benign	0.2879	benign	-0.465	Destabilizing	0.977	D	0.699	prob.neutral	None	None	None	None	N
V/N	0.8393	likely_pathogenic	0.8268	pathogenic	-1.018	Destabilizing	0.962	D	0.865	deleterious	None	None	None	None	N
V/P	0.5932	likely_pathogenic	0.5706	pathogenic	-0.708	Destabilizing	0.962	D	0.853	deleterious	None	None	None	None	N
V/Q	0.8442	likely_pathogenic	0.8372	pathogenic	-1.126	Destabilizing	0.992	D	0.855	deleterious	None	None	None	None	N
V/R	0.8707	likely_pathogenic	0.8561	pathogenic	-0.68	Destabilizing	0.997	D	0.863	deleterious	None	None	None	None	N
V/S	0.7138	likely_pathogenic	0.6652	pathogenic	-1.526	Destabilizing	0.985	D	0.82	deleterious	None	None	None	None	N
V/T	0.5478	ambiguous	0.4992	ambiguous	-1.39	Destabilizing	0.786	D	0.619	neutral	None	None	None	None	N
V/W	0.9433	likely_pathogenic	0.9256	pathogenic	-1.098	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
V/Y	0.8455	likely_pathogenic	0.816	pathogenic	-0.795	Destabilizing	0.997	D	0.813	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.