TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15812	47659;47660;47661	chr2:178617917;178617916;178617915	chr2:179482644;179482643;179482642
N2AB	14171	42736;42737;42738	chr2:178617917;178617916;178617915	chr2:179482644;179482643;179482642
N2A	13244	39955;39956;39957	chr2:178617917;178617916;178617915	chr2:179482644;179482643;179482642
N2B	6747	20464;20465;20466	chr2:178617917;178617916;178617915	chr2:179482644;179482643;179482642
Novex-1	6872	20839;20840;20841	chr2:178617917;178617916;178617915	chr2:179482644;179482643;179482642
Novex-2	6939	21040;21041;21042	chr2:178617917;178617916;178617915	chr2:179482644;179482643;179482642
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-2
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.4722
• 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
R/S	rs794729442	None	0.101	N	0.209	0.128	0.128392430309	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
R/S	rs794729442	None	0.101	N	0.209	0.128	0.128392430309	gnomAD-4.0.0	6.57964E-06	None	None	None	None	N	None	2.40813E-05	0	None	0	0	None	0	0	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
R/A	0.1707	likely_benign	0.1704	benign	-0.077	Destabilizing	0.061	N	0.138	neutral	None	None	None	None	N
R/C	0.2032	likely_benign	0.1796	benign	-0.144	Destabilizing	0.983	D	0.231	neutral	None	None	None	None	N
R/D	0.3155	likely_benign	0.3262	benign	-0.12	Destabilizing	0.418	N	0.289	neutral	None	None	None	None	N
R/E	0.222	likely_benign	0.2179	benign	-0.053	Destabilizing	0.129	N	0.203	neutral	None	None	None	None	N
R/F	0.4293	ambiguous	0.4178	ambiguous	-0.239	Destabilizing	0.94	D	0.282	neutral	None	None	None	None	N
R/G	0.1084	likely_benign	0.1108	benign	-0.291	Destabilizing	None	N	0.105	neutral	N	0.42399287	None	None	N
R/H	0.1056	likely_benign	0.1032	benign	-0.762	Destabilizing	0.836	D	0.361	neutral	None	None	None	None	N
R/I	0.2739	likely_benign	0.2601	benign	0.455	Stabilizing	0.351	N	0.371	neutral	N	0.469856515	None	None	N
R/K	0.0807	likely_benign	0.0802	benign	-0.161	Destabilizing	None	N	0.07	neutral	N	0.378390711	None	None	N
R/L	0.1608	likely_benign	0.1588	benign	0.455	Stabilizing	0.228	N	0.237	neutral	None	None	None	None	N
R/M	0.2115	likely_benign	0.2072	benign	0.068	Stabilizing	0.94	D	0.301	neutral	None	None	None	None	N
R/N	0.2593	likely_benign	0.2622	benign	0.153	Stabilizing	0.228	N	0.23	neutral	None	None	None	None	N
R/P	0.1578	likely_benign	0.1546	benign	0.299	Stabilizing	0.593	D	0.37	neutral	None	None	None	None	N
R/Q	0.0896	likely_benign	0.0901	benign	0.021	Stabilizing	0.264	N	0.303	neutral	None	None	None	None	N
R/S	0.2052	likely_benign	0.2079	benign	-0.234	Destabilizing	0.101	N	0.209	neutral	N	0.375682061	None	None	N
R/T	0.1425	likely_benign	0.1404	benign	-0.03	Destabilizing	0.003	N	0.124	neutral	N	0.406240357	None	None	N
R/V	0.2831	likely_benign	0.2667	benign	0.299	Stabilizing	0.418	N	0.324	neutral	None	None	None	None	N
R/W	0.2212	likely_benign	0.2111	benign	-0.234	Destabilizing	0.983	D	0.236	neutral	None	None	None	None	N
R/Y	0.3519	ambiguous	0.3396	benign	0.154	Stabilizing	0.94	D	0.315	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.