TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	975	3148;3149;3150	chr2:178782983;178782982;178782981	chr2:179647710;179647709;179647708
N2AB	975	3148;3149;3150	chr2:178782983;178782982;178782981	chr2:179647710;179647709;179647708
N2A	975	3148;3149;3150	chr2:178782983;178782982;178782981	chr2:179647710;179647709;179647708
N2B	929	3010;3011;3012	chr2:178782983;178782982;178782981	chr2:179647710;179647709;179647708
Novex-1	929	3010;3011;3012	chr2:178782983;178782982;178782981	chr2:179647710;179647709;179647708
Novex-2	929	3010;3011;3012	chr2:178782983;178782982;178782981	chr2:179647710;179647709;179647708
Novex-3	975	3148;3149;3150	chr2:178782983;178782982;178782981	chr2:179647710;179647709;179647708

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-3
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.2917
• 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
T/A	rs2092909709	None	None	N	0.165	0.216	0.238705975628	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	4.14422E-04	0
T/A	rs2092909709	None	None	N	0.165	0.216	0.238705975628	gnomAD-4.0.0	3.84149E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.02015E-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
T/A	0.1312	likely_benign	0.1351	benign	-1.0	Destabilizing	None	N	0.165	neutral	N	0.510637132	None	None	N
T/C	0.6007	likely_pathogenic	0.5965	pathogenic	-0.481	Destabilizing	0.667	D	0.507	neutral	None	None	None	None	N
T/D	0.6557	likely_pathogenic	0.672	pathogenic	-0.287	Destabilizing	0.364	N	0.523	neutral	None	None	None	None	N
T/E	0.4705	ambiguous	0.481	ambiguous	-0.214	Destabilizing	0.22	N	0.494	neutral	None	None	None	None	N
T/F	0.3447	ambiguous	0.3505	ambiguous	-0.827	Destabilizing	0.22	N	0.536	neutral	None	None	None	None	N
T/G	0.5079	ambiguous	0.5352	ambiguous	-1.336	Destabilizing	0.055	N	0.463	neutral	None	None	None	None	N
T/H	0.2874	likely_benign	0.2908	benign	-1.472	Destabilizing	0.859	D	0.545	neutral	None	None	None	None	N
T/I	0.1832	likely_benign	0.1813	benign	-0.168	Destabilizing	None	N	0.231	neutral	N	0.510162011	None	None	N
T/K	0.2029	likely_benign	0.1996	benign	-0.662	Destabilizing	0.175	N	0.475	neutral	N	0.502194723	None	None	N
T/L	0.1263	likely_benign	0.127	benign	-0.168	Destabilizing	None	N	0.231	neutral	None	None	None	None	N
T/M	0.0854	likely_benign	0.084	benign	0.034	Stabilizing	0.002	N	0.237	neutral	None	None	None	None	N
T/N	0.2073	likely_benign	0.206	benign	-0.794	Destabilizing	0.364	N	0.475	neutral	None	None	None	None	N
T/P	0.8775	likely_pathogenic	0.9069	pathogenic	-0.412	Destabilizing	0.301	N	0.522	neutral	D	0.667661124	None	None	N
T/Q	0.2495	likely_benign	0.2462	benign	-0.796	Destabilizing	0.22	N	0.551	neutral	None	None	None	None	N
T/R	0.168	likely_benign	0.1705	benign	-0.569	Destabilizing	0.175	N	0.523	neutral	N	0.486797195	None	None	N
T/S	0.1468	likely_benign	0.1489	benign	-1.125	Destabilizing	0.042	N	0.411	neutral	N	0.462418085	None	None	N
T/V	0.157	likely_benign	0.1587	benign	-0.412	Destabilizing	None	N	0.165	neutral	None	None	None	None	N
T/W	0.7223	likely_pathogenic	0.7393	pathogenic	-0.803	Destabilizing	0.958	D	0.554	neutral	None	None	None	None	N
T/Y	0.42	ambiguous	0.4195	ambiguous	-0.553	Destabilizing	0.667	D	0.59	neutral	None	None	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.