TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31512	94759;94760;94761	chr2:178546894;178546893;178546892	chr2:179411621;179411620;179411619
N2AB	29871	89836;89837;89838	chr2:178546894;178546893;178546892	chr2:179411621;179411620;179411619
N2A	28944	87055;87056;87057	chr2:178546894;178546893;178546892	chr2:179411621;179411620;179411619
N2B	22447	67564;67565;67566	chr2:178546894;178546893;178546892	chr2:179411621;179411620;179411619
Novex-1	22572	67939;67940;67941	chr2:178546894;178546893;178546892	chr2:179411621;179411620;179411619
Novex-2	22639	68140;68141;68142	chr2:178546894;178546893;178546892	chr2:179411621;179411620;179411619
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-118
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.55
• 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
R/K	rs1186432203	-0.492	0.002	N	0.153	0.107	0.243398259712	gnomAD-2.1.1	4.38E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.94E-05	None	0	0	0
R/K	rs1186432203	-0.492	0.002	N	0.153	0.107	0.243398259712	gnomAD-4.0.0	2.09324E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.13212E-07	2.43849E-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
R/A	0.3783	ambiguous	0.3062	benign	-0.552	Destabilizing	0.688	D	0.447	neutral	None	None	None	None	N
R/C	0.1504	likely_benign	0.1265	benign	-0.498	Destabilizing	0.998	D	0.511	neutral	None	None	None	None	N
R/D	0.7945	likely_pathogenic	0.6865	pathogenic	-0.09	Destabilizing	0.842	D	0.514	neutral	None	None	None	None	N
R/E	0.4324	ambiguous	0.3478	ambiguous	-0.02	Destabilizing	0.525	D	0.456	neutral	None	None	None	None	N
R/F	0.5097	ambiguous	0.4187	ambiguous	-0.712	Destabilizing	0.991	D	0.52	neutral	None	None	None	None	N
R/G	0.3773	ambiguous	0.2957	benign	-0.781	Destabilizing	0.801	D	0.482	neutral	N	0.478362976	None	None	N
R/H	0.1099	likely_benign	0.095	benign	-1.165	Destabilizing	0.991	D	0.565	neutral	None	None	None	None	N
R/I	0.2286	likely_benign	0.19	benign	0.035	Stabilizing	0.934	D	0.522	neutral	N	0.513227698	None	None	N
R/K	0.0838	likely_benign	0.0693	benign	-0.562	Destabilizing	0.002	N	0.153	neutral	N	0.390861421	None	None	N
R/L	0.1864	likely_benign	0.173	benign	0.035	Stabilizing	0.842	D	0.455	neutral	None	None	None	None	N
R/M	0.2396	likely_benign	0.1992	benign	-0.159	Destabilizing	0.991	D	0.545	neutral	None	None	None	None	N
R/N	0.6239	likely_pathogenic	0.487	ambiguous	-0.035	Destabilizing	0.842	D	0.467	neutral	None	None	None	None	N
R/P	0.4079	ambiguous	0.3498	ambiguous	-0.14	Destabilizing	0.974	D	0.529	neutral	None	None	None	None	N
R/Q	0.0989	likely_benign	0.0929	benign	-0.286	Destabilizing	0.842	D	0.551	neutral	None	None	None	None	N
R/S	0.504	ambiguous	0.4035	ambiguous	-0.675	Destabilizing	0.454	N	0.45	neutral	N	0.467167334	None	None	N
R/T	0.2084	likely_benign	0.1752	benign	-0.458	Destabilizing	0.051	N	0.278	neutral	N	0.422453765	None	None	N
R/V	0.2831	likely_benign	0.2476	benign	-0.14	Destabilizing	0.842	D	0.517	neutral	None	None	None	None	N
R/W	0.2184	likely_benign	0.1918	benign	-0.53	Destabilizing	0.998	D	0.577	neutral	None	None	None	None	N
R/Y	0.4001	ambiguous	0.3183	benign	-0.177	Destabilizing	0.991	D	0.53	neutral	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.