TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28694	86305;86306;86307	chr2:178560052;178560051;178560050	chr2:179424779;179424778;179424777
N2AB	27053	81382;81383;81384	chr2:178560052;178560051;178560050	chr2:179424779;179424778;179424777
N2A	26126	78601;78602;78603	chr2:178560052;178560051;178560050	chr2:179424779;179424778;179424777
N2B	19629	59110;59111;59112	chr2:178560052;178560051;178560050	chr2:179424779;179424778;179424777
Novex-1	19754	59485;59486;59487	chr2:178560052;178560051;178560050	chr2:179424779;179424778;179424777
Novex-2	19821	59686;59687;59688	chr2:178560052;178560051;178560050	chr2:179424779;179424778;179424777
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: Fn3-97
• Domain position: 44
• Structural Position: 54
• Q(SASA): 0.9708
• 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/H	None	None	0.295	N	0.196	0.157	0.289098819767	gnomAD-4.0.0	6.84256E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99454E-07	0	0
D/N	rs796298969	None	0.001	N	0.225	0.119	0.231873229951	gnomAD-4.0.0	4.78979E-06	None	None	None	None	N	None	8.96164E-05	0	None	0	0	None	0	0	3.59781E-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
D/A	0.0969	likely_benign	0.0964	benign	-0.11	Destabilizing	0.012	N	0.278	neutral	N	0.458107921	None	None	N
D/C	0.3841	ambiguous	0.3506	ambiguous	0.034	Stabilizing	0.864	D	0.185	neutral	None	None	None	None	N
D/E	0.0963	likely_benign	0.093	benign	-0.284	Destabilizing	None	N	0.179	neutral	N	0.47396002	None	None	N
D/F	0.4391	ambiguous	0.4183	ambiguous	-0.215	Destabilizing	0.214	N	0.222	neutral	None	None	None	None	N
D/G	0.082	likely_benign	0.0827	benign	-0.233	Destabilizing	0.012	N	0.249	neutral	N	0.415853079	None	None	N
D/H	0.1762	likely_benign	0.1787	benign	0.222	Stabilizing	0.295	N	0.196	neutral	N	0.503437565	None	None	N
D/I	0.2126	likely_benign	0.2027	benign	0.15	Stabilizing	0.038	N	0.242	neutral	None	None	None	None	N
D/K	0.1844	likely_benign	0.1818	benign	0.472	Stabilizing	0.038	N	0.239	neutral	None	None	None	None	N
D/L	0.2312	likely_benign	0.2184	benign	0.15	Stabilizing	None	N	0.282	neutral	None	None	None	None	N
D/M	0.3546	ambiguous	0.3398	benign	0.14	Stabilizing	0.214	N	0.189	neutral	None	None	None	None	N
D/N	0.0724	likely_benign	0.0731	benign	0.254	Stabilizing	0.001	N	0.225	neutral	N	0.45077373	None	None	N
D/P	0.46	ambiguous	0.4586	ambiguous	0.083	Stabilizing	0.356	N	0.242	neutral	None	None	None	None	N
D/Q	0.1788	likely_benign	0.173	benign	0.246	Stabilizing	0.038	N	0.191	neutral	None	None	None	None	N
D/R	0.2287	likely_benign	0.2219	benign	0.63	Stabilizing	0.12	N	0.26	neutral	None	None	None	None	N
D/S	0.072	likely_benign	0.0732	benign	0.159	Stabilizing	None	N	0.159	neutral	None	None	None	None	N
D/T	0.1103	likely_benign	0.107	benign	0.256	Stabilizing	0.016	N	0.235	neutral	None	None	None	None	N
D/V	0.1381	likely_benign	0.134	benign	0.083	Stabilizing	0.001	N	0.277	neutral	N	0.488545471	None	None	N
D/W	0.7541	likely_pathogenic	0.743	pathogenic	-0.154	Destabilizing	0.864	D	0.263	neutral	None	None	None	None	N
D/Y	0.1953	likely_benign	0.1975	benign	0.012	Stabilizing	0.56	D	0.215	neutral	N	0.47541139	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.