TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2573	7942;7943;7944	chr2:178773247;178773246;178773245	chr2:179637974;179637973;179637972
N2AB	2573	7942;7943;7944	chr2:178773247;178773246;178773245	chr2:179637974;179637973;179637972
N2A	2573	7942;7943;7944	chr2:178773247;178773246;178773245	chr2:179637974;179637973;179637972
N2B	2527	7804;7805;7806	chr2:178773247;178773246;178773245	chr2:179637974;179637973;179637972
Novex-1	2527	7804;7805;7806	chr2:178773247;178773246;178773245	chr2:179637974;179637973;179637972
Novex-2	2527	7804;7805;7806	chr2:178773247;178773246;178773245	chr2:179637974;179637973;179637972
Novex-3	2573	7942;7943;7944	chr2:178773247;178773246;178773245	chr2:179637974;179637973;179637972

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-15
• Domain position: 41
• Structural Position: 59
• Q(SASA): 0.6614
• 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
K/N	rs2091795391	None	0.22	D	0.447	0.162	0.191931220699	gnomAD-4.0.0	6.84166E-07	None	None	None	None	N	None	0	2.23774E-05	None	0	0	None	0	0	0	0	0
K/R	rs113405975	None	0.124	N	0.483	0.201	0.359557344763	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.2885	likely_benign	0.3105	benign	-0.027	Destabilizing	0.072	N	0.497	neutral	None	None	None	None	N
K/C	0.6831	likely_pathogenic	0.7165	pathogenic	-0.494	Destabilizing	0.968	D	0.578	neutral	None	None	None	None	N
K/D	0.6182	likely_pathogenic	0.6156	pathogenic	-0.135	Destabilizing	0.272	N	0.506	neutral	None	None	None	None	N
K/E	0.1859	likely_benign	0.1919	benign	-0.11	Destabilizing	0.124	N	0.52	neutral	N	0.509704734	None	None	N
K/F	0.6248	likely_pathogenic	0.6321	pathogenic	-0.249	Destabilizing	0.396	N	0.573	neutral	None	None	None	None	N
K/G	0.4555	ambiguous	0.4803	ambiguous	-0.212	Destabilizing	0.157	N	0.527	neutral	None	None	None	None	N
K/H	0.2912	likely_benign	0.3178	benign	-0.329	Destabilizing	0.567	D	0.501	neutral	None	None	None	None	N
K/I	0.2541	likely_benign	0.2491	benign	0.384	Stabilizing	0.567	D	0.574	neutral	None	None	None	None	N
K/L	0.2639	likely_benign	0.274	benign	0.384	Stabilizing	0.157	N	0.527	neutral	None	None	None	None	N
K/M	0.2019	likely_benign	0.215	benign	-0.096	Destabilizing	0.883	D	0.493	neutral	D	0.654529429	None	None	N
K/N	0.3958	ambiguous	0.3842	ambiguous	-0.114	Destabilizing	0.22	N	0.447	neutral	D	0.646371903	None	None	N
K/P	0.5253	ambiguous	0.5544	ambiguous	0.273	Stabilizing	0.726	D	0.501	neutral	None	None	None	None	N
K/Q	0.1223	likely_benign	0.136	benign	-0.182	Destabilizing	0.002	N	0.207	neutral	N	0.512486055	None	None	N
K/R	0.0977	likely_benign	0.1044	benign	-0.135	Destabilizing	0.124	N	0.483	neutral	N	0.512076177	None	None	N
K/S	0.3505	ambiguous	0.3548	ambiguous	-0.501	Destabilizing	0.005	N	0.205	neutral	None	None	None	None	N
K/T	0.1494	likely_benign	0.1558	benign	-0.331	Destabilizing	0.124	N	0.523	neutral	D	0.542577253	None	None	N
K/V	0.2652	likely_benign	0.2695	benign	0.273	Stabilizing	0.567	D	0.496	neutral	None	None	None	None	N
K/W	0.7695	likely_pathogenic	0.7843	pathogenic	-0.347	Destabilizing	0.909	D	0.579	neutral	None	None	None	None	N
K/Y	0.5596	ambiguous	0.5661	pathogenic	0.01	Stabilizing	0.003	N	0.317	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.