TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3898	11917;11918;11919	chr2:178741541;178741540;178741539	chr2:179606268;179606267;179606266
N2AB	3581	10966;10967;10968	chr2:178741541;178741540;178741539	chr2:179606268;179606267;179606266
N2A	None	None	chr2:None	chr2:None
N2B	3535	10828;10829;10830	chr2:178741541;178741540;178741539	chr2:179606268;179606267;179606266
Novex-1	3660	11203;11204;11205	chr2:178741541;178741540;178741539	chr2:179606268;179606267;179606266
Novex-2	3727	11404;11405;11406	chr2:178741541;178741540;178741539	chr2:179606268;179606267;179606266
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: Ig-27
• Domain position: 79
• Structural Position: 163
• Q(SASA): 0.9965
• 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/C	rs747933911	0.324	0.987	N	0.507	0.339	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
Y/C	rs747933911	0.324	0.987	N	0.507	0.339	None	gnomAD-4.0.0	1.59116E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85801E-06	0	0
Y/D	rs1553941743	None	0.326	N	0.493	0.324	None	gnomAD-4.0.0	4.77348E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.57403E-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	0.4409	ambiguous	0.3851	ambiguous	-0.455	Destabilizing	0.345	N	0.529	neutral	None	None	None	None	I
Y/C	0.112	likely_benign	0.1096	benign	0.283	Stabilizing	0.987	D	0.507	neutral	N	0.509689058	None	None	I
Y/D	0.1689	likely_benign	0.1732	benign	0.767	Stabilizing	0.326	N	0.493	neutral	N	0.51008613	None	None	I
Y/E	0.5377	ambiguous	0.4955	ambiguous	0.738	Stabilizing	0.345	N	0.484	neutral	None	None	None	None	I
Y/F	0.1329	likely_benign	0.11	benign	-0.276	Destabilizing	0.001	N	0.257	neutral	N	0.400155286	None	None	I
Y/G	0.3648	ambiguous	0.3565	ambiguous	-0.628	Destabilizing	0.209	N	0.513	neutral	None	None	None	None	I
Y/H	0.1359	likely_benign	0.1176	benign	0.256	Stabilizing	0.001	N	0.269	neutral	N	0.442132062	None	None	I
Y/I	0.4569	ambiguous	0.4167	ambiguous	-0.03	Destabilizing	0.561	D	0.505	neutral	None	None	None	None	I
Y/K	0.4428	ambiguous	0.3914	ambiguous	0.32	Stabilizing	0.561	D	0.499	neutral	None	None	None	None	I
Y/L	0.4526	ambiguous	0.4326	ambiguous	-0.03	Destabilizing	0.209	N	0.485	neutral	None	None	None	None	I
Y/M	0.6156	likely_pathogenic	0.5911	pathogenic	0.024	Stabilizing	0.965	D	0.507	neutral	None	None	None	None	I
Y/N	0.1191	likely_benign	0.1113	benign	0.151	Stabilizing	0.001	N	0.404	neutral	N	0.469938544	None	None	I
Y/P	0.8836	likely_pathogenic	0.9022	pathogenic	-0.152	Destabilizing	0.965	D	0.519	neutral	None	None	None	None	I
Y/Q	0.4324	ambiguous	0.3737	ambiguous	0.195	Stabilizing	0.561	D	0.499	neutral	None	None	None	None	I
Y/R	0.279	likely_benign	0.2505	benign	0.5	Stabilizing	0.561	D	0.537	neutral	None	None	None	None	I
Y/S	0.1602	likely_benign	0.1459	benign	-0.189	Destabilizing	0.166	N	0.505	neutral	N	0.474184349	None	None	I
Y/T	0.3942	ambiguous	0.3611	ambiguous	-0.126	Destabilizing	0.561	D	0.499	neutral	None	None	None	None	I
Y/V	0.3812	ambiguous	0.3504	ambiguous	-0.152	Destabilizing	0.561	D	0.469	neutral	None	None	None	None	I
Y/W	0.4572	ambiguous	0.4632	ambiguous	-0.482	Destabilizing	0.965	D	0.476	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.