TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31954	96085;96086;96087	chr2:178544369;178544368;178544367	chr2:179409096;179409095;179409094
N2AB	30313	91162;91163;91164	chr2:178544369;178544368;178544367	chr2:179409096;179409095;179409094
N2A	29386	88381;88382;88383	chr2:178544369;178544368;178544367	chr2:179409096;179409095;179409094
N2B	22889	68890;68891;68892	chr2:178544369;178544368;178544367	chr2:179409096;179409095;179409094
Novex-1	23014	69265;69266;69267	chr2:178544369;178544368;178544367	chr2:179409096;179409095;179409094
Novex-2	23081	69466;69467;69468	chr2:178544369;178544368;178544367	chr2:179409096;179409095;179409094
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-121
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.8897
• 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
D/E	rs765845110	0.05	0.001	N	0.077	0.077	0.0716867268079	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	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
D/A	0.0934	likely_benign	0.092	benign	0.074	Stabilizing	0.201	N	0.34	neutral	N	0.487214532	None	None	N
D/C	0.3535	ambiguous	0.3511	ambiguous	-0.034	Destabilizing	0.992	D	0.357	neutral	None	None	None	None	N
D/E	0.0801	likely_benign	0.0817	benign	-0.31	Destabilizing	0.001	N	0.077	neutral	N	0.418525238	None	None	N
D/F	0.391	ambiguous	0.3845	ambiguous	-0.109	Destabilizing	0.972	D	0.365	neutral	None	None	None	None	N
D/G	0.0855	likely_benign	0.0822	benign	-0.018	Destabilizing	0.549	D	0.385	neutral	N	0.440727307	None	None	N
D/H	0.1749	likely_benign	0.1652	benign	0.451	Stabilizing	0.896	D	0.379	neutral	N	0.508821955	None	None	N
D/I	0.1971	likely_benign	0.1853	benign	0.242	Stabilizing	0.92	D	0.378	neutral	None	None	None	None	N
D/K	0.1476	likely_benign	0.1385	benign	0.469	Stabilizing	0.25	N	0.4	neutral	None	None	None	None	N
D/L	0.1881	likely_benign	0.1831	benign	0.242	Stabilizing	0.617	D	0.357	neutral	None	None	None	None	N
D/M	0.3282	likely_benign	0.3231	benign	0.087	Stabilizing	0.992	D	0.359	neutral	None	None	None	None	N
D/N	0.0754	likely_benign	0.0738	benign	0.344	Stabilizing	0.549	D	0.293	neutral	N	0.465991111	None	None	N
D/P	0.2818	likely_benign	0.2738	benign	0.204	Stabilizing	0.766	D	0.385	neutral	None	None	None	None	N
D/Q	0.1572	likely_benign	0.1513	benign	0.319	Stabilizing	0.059	N	0.201	neutral	None	None	None	None	N
D/R	0.1993	likely_benign	0.1836	benign	0.634	Stabilizing	0.617	D	0.376	neutral	None	None	None	None	N
D/S	0.0768	likely_benign	0.075	benign	0.231	Stabilizing	0.25	N	0.315	neutral	None	None	None	None	N
D/T	0.1194	likely_benign	0.1169	benign	0.304	Stabilizing	0.617	D	0.359	neutral	None	None	None	None	N
D/V	0.1245	likely_benign	0.1184	benign	0.204	Stabilizing	0.549	D	0.358	neutral	N	0.494217862	None	None	N
D/W	0.7212	likely_pathogenic	0.7073	pathogenic	-0.103	Destabilizing	0.992	D	0.392	neutral	None	None	None	None	N
D/Y	0.177	likely_benign	0.1705	benign	0.11	Stabilizing	0.963	D	0.365	neutral	N	0.508475239	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.