TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28081	84466;84467;84468	chr2:178561891;178561890;178561889	chr2:179426618;179426617;179426616
N2AB	26440	79543;79544;79545	chr2:178561891;178561890;178561889	chr2:179426618;179426617;179426616
N2A	25513	76762;76763;76764	chr2:178561891;178561890;178561889	chr2:179426618;179426617;179426616
N2B	19016	57271;57272;57273	chr2:178561891;178561890;178561889	chr2:179426618;179426617;179426616
Novex-1	19141	57646;57647;57648	chr2:178561891;178561890;178561889	chr2:179426618;179426617;179426616
Novex-2	19208	57847;57848;57849	chr2:178561891;178561890;178561889	chr2:179426618;179426617;179426616
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-92
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.9186
• 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
Y/S	None	None	0.967	N	0.465	0.43	0.454798141022	gnomAD-4.0.0	1.59178E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85865E-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
Y/A	0.791	likely_pathogenic	0.7867	pathogenic	-0.883	Destabilizing	0.916	D	0.487	neutral	None	None	None	None	I
Y/C	0.4625	ambiguous	0.4545	ambiguous	0.029	Stabilizing	0.999	D	0.645	neutral	N	0.498975559	None	None	I
Y/D	0.3057	likely_benign	0.3393	benign	0.918	Stabilizing	0.025	N	0.493	neutral	N	0.400243335	None	None	I
Y/E	0.7664	likely_pathogenic	0.7684	pathogenic	0.903	Stabilizing	0.845	D	0.484	neutral	None	None	None	None	I
Y/F	0.1647	likely_benign	0.1554	benign	-0.465	Destabilizing	0.981	D	0.519	neutral	N	0.500428972	None	None	I
Y/G	0.6611	likely_pathogenic	0.6556	pathogenic	-1.078	Destabilizing	0.975	D	0.519	neutral	None	None	None	None	I
Y/H	0.491	ambiguous	0.4712	ambiguous	0.099	Stabilizing	0.994	D	0.57	neutral	N	0.507066943	None	None	I
Y/I	0.7446	likely_pathogenic	0.7078	pathogenic	-0.388	Destabilizing	0.987	D	0.574	neutral	None	None	None	None	I
Y/K	0.8406	likely_pathogenic	0.8163	pathogenic	0.113	Stabilizing	0.975	D	0.601	neutral	None	None	None	None	I
Y/L	0.697	likely_pathogenic	0.6516	pathogenic	-0.388	Destabilizing	0.957	D	0.547	neutral	None	None	None	None	I
Y/M	0.7518	likely_pathogenic	0.7239	pathogenic	-0.14	Destabilizing	0.999	D	0.565	neutral	None	None	None	None	I
Y/N	0.2071	likely_benign	0.2166	benign	-0.059	Destabilizing	0.935	D	0.605	neutral	N	0.511144611	None	None	I
Y/P	0.98	likely_pathogenic	0.9779	pathogenic	-0.534	Destabilizing	0.987	D	0.648	neutral	None	None	None	None	I
Y/Q	0.8125	likely_pathogenic	0.796	pathogenic	-0.04	Destabilizing	0.987	D	0.563	neutral	None	None	None	None	I
Y/R	0.7894	likely_pathogenic	0.7659	pathogenic	0.437	Stabilizing	0.987	D	0.603	neutral	None	None	None	None	I
Y/S	0.458	ambiguous	0.4692	ambiguous	-0.55	Destabilizing	0.967	D	0.465	neutral	N	0.476397319	None	None	I
Y/T	0.6754	likely_pathogenic	0.6443	pathogenic	-0.476	Destabilizing	0.975	D	0.559	neutral	None	None	None	None	I
Y/V	0.6531	likely_pathogenic	0.6251	pathogenic	-0.534	Destabilizing	0.987	D	0.509	neutral	None	None	None	None	I
Y/W	0.6525	likely_pathogenic	0.6362	pathogenic	-0.52	Destabilizing	0.999	D	0.549	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.