TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22357	67294;67295;67296	chr2:178580218;178580217;178580216	chr2:179444945;179444944;179444943
N2AB	20716	62371;62372;62373	chr2:178580218;178580217;178580216	chr2:179444945;179444944;179444943
N2A	19789	59590;59591;59592	chr2:178580218;178580217;178580216	chr2:179444945;179444944;179444943
N2B	13292	40099;40100;40101	chr2:178580218;178580217;178580216	chr2:179444945;179444944;179444943
Novex-1	13417	40474;40475;40476	chr2:178580218;178580217;178580216	chr2:179444945;179444944;179444943
Novex-2	13484	40675;40676;40677	chr2:178580218;178580217;178580216	chr2:179444945;179444944;179444943
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: Fn3-50
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.321
• 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/S	rs1446351991	-1.29	1.0	N	0.805	0.487	0.405560941015	gnomAD-2.1.1	8.08E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
P/S	rs1446351991	-1.29	1.0	N	0.805	0.487	0.405560941015	gnomAD-4.0.0	7.53261E-06	None	None	None	None	I	None	2.9967E-05	0	None	0	0	None	0	0	8.99798E-06	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
P/A	0.1101	likely_benign	0.116	benign	-1.521	Destabilizing	1.0	D	0.808	deleterious	N	0.45615812	None	None	I
P/C	0.6344	likely_pathogenic	0.653	pathogenic	-0.961	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
P/D	0.8781	likely_pathogenic	0.8992	pathogenic	-1.656	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
P/E	0.6148	likely_pathogenic	0.6361	pathogenic	-1.688	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
P/F	0.7434	likely_pathogenic	0.7743	pathogenic	-1.297	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	I
P/G	0.6166	likely_pathogenic	0.6469	pathogenic	-1.807	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	I
P/H	0.4932	ambiguous	0.5415	ambiguous	-1.348	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	I
P/I	0.5028	ambiguous	0.5529	ambiguous	-0.839	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	I
P/K	0.5439	ambiguous	0.581	pathogenic	-1.228	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
P/L	0.2829	likely_benign	0.3228	benign	-0.839	Destabilizing	1.0	D	0.874	deleterious	D	0.546195796	None	None	I
P/M	0.4869	ambiguous	0.5055	ambiguous	-0.568	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	I
P/N	0.7101	likely_pathogenic	0.7295	pathogenic	-0.966	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	I
P/Q	0.329	likely_benign	0.361	ambiguous	-1.221	Destabilizing	1.0	D	0.841	deleterious	N	0.517923323	None	None	I
P/R	0.4235	ambiguous	0.4696	ambiguous	-0.637	Destabilizing	1.0	D	0.889	deleterious	N	0.512834441	None	None	I
P/S	0.2679	likely_benign	0.2938	benign	-1.415	Destabilizing	1.0	D	0.805	deleterious	N	0.500717667	None	None	I
P/T	0.2893	likely_benign	0.3359	benign	-1.352	Destabilizing	1.0	D	0.81	deleterious	N	0.519190771	None	None	I
P/V	0.3807	ambiguous	0.4143	ambiguous	-1.033	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	I
P/W	0.9158	likely_pathogenic	0.9377	pathogenic	-1.453	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
P/Y	0.7552	likely_pathogenic	0.7956	pathogenic	-1.189	Destabilizing	1.0	D	0.893	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.