TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8614	26065;26066;26067	chr2:178715574;178715573;178715572	chr2:179580301;179580300;179580299
N2AB	8297	25114;25115;25116	chr2:178715574;178715573;178715572	chr2:179580301;179580300;179580299
N2A	7370	22333;22334;22335	chr2:178715574;178715573;178715572	chr2:179580301;179580300;179580299
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: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-71
• Domain position: 66
• Structural Position: 146
• Q(SASA): 0.6972
• 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	0.202	N	0.175	0.072	0.220303561663	gnomAD-4.0.0	1.59153E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43283E-05	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	0.1166	likely_benign	0.1102	benign	-0.706	Destabilizing	0.202	N	0.175	neutral	N	0.443663251	None	None	I
V/C	0.7045	likely_pathogenic	0.7022	pathogenic	-0.664	Destabilizing	0.985	D	0.273	neutral	None	None	None	None	I
V/D	0.3023	likely_benign	0.2763	benign	-0.484	Destabilizing	0.97	D	0.356	neutral	N	0.511408396	None	None	I
V/E	0.208	likely_benign	0.1983	benign	-0.604	Destabilizing	0.875	D	0.327	neutral	None	None	None	None	I
V/F	0.1513	likely_benign	0.1423	benign	-0.948	Destabilizing	0.001	N	0.177	neutral	N	0.487531458	None	None	I
V/G	0.1823	likely_benign	0.178	benign	-0.849	Destabilizing	0.927	D	0.348	neutral	N	0.502692912	None	None	I
V/H	0.4611	ambiguous	0.4408	ambiguous	-0.37	Destabilizing	0.885	D	0.329	neutral	None	None	None	None	I
V/I	0.071	likely_benign	0.0692	benign	-0.477	Destabilizing	None	N	0.215	neutral	N	0.45486168	None	None	I
V/K	0.2258	likely_benign	0.2177	benign	-0.486	Destabilizing	0.834	D	0.323	neutral	None	None	None	None	I
V/L	0.1362	likely_benign	0.1295	benign	-0.477	Destabilizing	None	N	0.089	neutral	N	0.423863982	None	None	I
V/M	0.1016	likely_benign	0.099	benign	-0.311	Destabilizing	0.791	D	0.278	neutral	None	None	None	None	I
V/N	0.2301	likely_benign	0.2136	benign	-0.219	Destabilizing	0.695	D	0.353	neutral	None	None	None	None	I
V/P	0.281	likely_benign	0.2556	benign	-0.518	Destabilizing	0.695	D	0.329	neutral	None	None	None	None	I
V/Q	0.2351	likely_benign	0.2313	benign	-0.531	Destabilizing	0.916	D	0.319	neutral	None	None	None	None	I
V/R	0.1915	likely_benign	0.1885	benign	0.099	Stabilizing	0.97	D	0.354	neutral	None	None	None	None	I
V/S	0.1613	likely_benign	0.1501	benign	-0.617	Destabilizing	0.623	D	0.3	neutral	None	None	None	None	I
V/T	0.1079	likely_benign	0.1008	benign	-0.639	Destabilizing	0.247	N	0.153	neutral	None	None	None	None	I
V/W	0.6399	likely_pathogenic	0.6279	pathogenic	-0.983	Destabilizing	0.997	D	0.343	neutral	None	None	None	None	I
V/Y	0.465	ambiguous	0.441	ambiguous	-0.682	Destabilizing	0.02	N	0.19	neutral	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.