TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28553	85882;85883;85884	chr2:178560475;178560474;178560473	chr2:179425202;179425201;179425200
N2AB	26912	80959;80960;80961	chr2:178560475;178560474;178560473	chr2:179425202;179425201;179425200
N2A	25985	78178;78179;78180	chr2:178560475;178560474;178560473	chr2:179425202;179425201;179425200
N2B	19488	58687;58688;58689	chr2:178560475;178560474;178560473	chr2:179425202;179425201;179425200
Novex-1	19613	59062;59063;59064	chr2:178560475;178560474;178560473	chr2:179425202;179425201;179425200
Novex-2	19680	59263;59264;59265	chr2:178560475;178560474;178560473	chr2:179425202;179425201;179425200
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-96
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2487
• 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
P/L	rs1303551225	-0.752	0.822	D	0.815	0.401	0.413241256734	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	1.9305E-04	None	0	0	0	2.07297E-04	0
P/L	rs1303551225	-0.752	0.822	D	0.815	0.401	0.413241256734	gnomAD-4.0.0	5.12755E-06	None	None	None	None	I	None	0	0	None	0	7.29359E-05	None	0	0	0	1.34117E-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
P/A	0.0592	likely_benign	0.0615	benign	-1.513	Destabilizing	0.025	N	0.365	neutral	N	0.470434139	None	None	I
P/C	0.3783	ambiguous	0.3727	ambiguous	-1.298	Destabilizing	0.998	D	0.849	deleterious	None	None	None	None	I
P/D	0.6934	likely_pathogenic	0.6986	pathogenic	-1.778	Destabilizing	0.956	D	0.734	prob.delet.	None	None	None	None	I
P/E	0.3031	likely_benign	0.3013	benign	-1.806	Destabilizing	0.754	D	0.705	prob.neutral	None	None	None	None	I
P/F	0.4933	ambiguous	0.476	ambiguous	-1.415	Destabilizing	0.993	D	0.86	deleterious	None	None	None	None	I
P/G	0.3368	likely_benign	0.3415	ambiguous	-1.781	Destabilizing	0.754	D	0.773	deleterious	None	None	None	None	I
P/H	0.2273	likely_benign	0.2358	benign	-1.243	Destabilizing	0.994	D	0.825	deleterious	None	None	None	None	I
P/I	0.3241	likely_benign	0.2975	benign	-0.884	Destabilizing	0.978	D	0.837	deleterious	None	None	None	None	I
P/K	0.2512	likely_benign	0.2542	benign	-1.152	Destabilizing	0.019	N	0.421	neutral	None	None	None	None	I
P/L	0.1543	likely_benign	0.1472	benign	-0.884	Destabilizing	0.822	D	0.815	deleterious	D	0.530395718	None	None	I
P/M	0.3064	likely_benign	0.2929	benign	-0.723	Destabilizing	0.998	D	0.825	deleterious	None	None	None	None	I
P/N	0.476	ambiguous	0.4814	ambiguous	-1.023	Destabilizing	0.956	D	0.798	deleterious	None	None	None	None	I
P/Q	0.1346	likely_benign	0.1416	benign	-1.303	Destabilizing	0.942	D	0.736	prob.delet.	N	0.485994001	None	None	I
P/R	0.1582	likely_benign	0.1619	benign	-0.583	Destabilizing	0.89	D	0.808	deleterious	N	0.506251076	None	None	I
P/S	0.1153	likely_benign	0.1183	benign	-1.499	Destabilizing	0.698	D	0.702	prob.neutral	D	0.525466276	None	None	I
P/T	0.1374	likely_benign	0.1384	benign	-1.426	Destabilizing	0.822	D	0.713	prob.delet.	N	0.511784484	None	None	I
P/V	0.2017	likely_benign	0.1889	benign	-1.061	Destabilizing	0.86	D	0.787	deleterious	None	None	None	None	I
P/W	0.7306	likely_pathogenic	0.7099	pathogenic	-1.528	Destabilizing	0.998	D	0.858	deleterious	None	None	None	None	I
P/Y	0.4864	ambiguous	0.48	ambiguous	-1.225	Destabilizing	0.993	D	0.856	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.