TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28543	85852;85853;85854	chr2:178560505;178560504;178560503	chr2:179425232;179425231;179425230
N2AB	26902	80929;80930;80931	chr2:178560505;178560504;178560503	chr2:179425232;179425231;179425230
N2A	25975	78148;78149;78150	chr2:178560505;178560504;178560503	chr2:179425232;179425231;179425230
N2B	19478	58657;58658;58659	chr2:178560505;178560504;178560503	chr2:179425232;179425231;179425230
Novex-1	19603	59032;59033;59034	chr2:178560505;178560504;178560503	chr2:179425232;179425231;179425230
Novex-2	19670	59233;59234;59235	chr2:178560505;178560504;178560503	chr2:179425232;179425231;179425230
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-95
• Domain position: 94
• Structural Position: 129
• Q(SASA): 0.3943
• 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/E	None	None	0.007	N	0.336	0.161	0.280987212366	gnomAD-4.0.0	1.36907E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99758E-07	0	1.65755E-05

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	0.4408	ambiguous	0.4189	ambiguous	-0.391	Destabilizing	0.74	D	0.666	prob.neutral	None	None	None	None	N
K/C	0.6445	likely_pathogenic	0.6445	pathogenic	-0.531	Destabilizing	0.996	D	0.855	deleterious	None	None	None	None	N
K/D	0.7573	likely_pathogenic	0.7429	pathogenic	0.2	Stabilizing	0.587	D	0.734	deleterious	None	None	None	None	N
K/E	0.2183	likely_benign	0.2017	benign	0.302	Stabilizing	0.007	N	0.336	neutral	N	0.483914675	None	None	N
K/F	0.8163	likely_pathogenic	0.8146	pathogenic	-0.122	Destabilizing	0.984	D	0.821	deleterious	None	None	None	None	N
K/G	0.6878	likely_pathogenic	0.6685	pathogenic	-0.725	Destabilizing	0.74	D	0.704	prob.delet.	None	None	None	None	N
K/H	0.3791	ambiguous	0.3829	ambiguous	-0.872	Destabilizing	0.953	D	0.757	deleterious	None	None	None	None	N
K/I	0.3056	likely_benign	0.3009	benign	0.457	Stabilizing	0.953	D	0.828	deleterious	None	None	None	None	N
K/L	0.3462	ambiguous	0.3357	benign	0.457	Stabilizing	0.74	D	0.7	prob.delet.	None	None	None	None	N
K/M	0.2264	likely_benign	0.2168	benign	0.133	Stabilizing	0.994	D	0.755	deleterious	N	0.484928634	None	None	N
K/N	0.5762	likely_pathogenic	0.5644	pathogenic	-0.264	Destabilizing	0.883	D	0.624	neutral	N	0.484928634	None	None	N
K/P	0.7068	likely_pathogenic	0.6688	pathogenic	0.205	Stabilizing	0.953	D	0.741	deleterious	None	None	None	None	N
K/Q	0.1634	likely_benign	0.1588	benign	-0.3	Destabilizing	0.162	N	0.377	neutral	D	0.525858639	None	None	N
K/R	0.0879	likely_benign	0.0897	benign	-0.337	Destabilizing	0.028	N	0.337	neutral	N	0.506656803	None	None	N
K/S	0.5781	likely_pathogenic	0.5589	ambiguous	-0.915	Destabilizing	0.74	D	0.556	neutral	None	None	None	None	N
K/T	0.1768	likely_benign	0.169	benign	-0.612	Destabilizing	0.682	D	0.733	deleterious	N	0.504576503	None	None	N
K/V	0.2712	likely_benign	0.2658	benign	0.205	Stabilizing	0.953	D	0.655	prob.neutral	None	None	None	None	N
K/W	0.7835	likely_pathogenic	0.7782	pathogenic	-0.029	Destabilizing	0.996	D	0.83	deleterious	None	None	None	None	N
K/Y	0.681	likely_pathogenic	0.6728	pathogenic	0.261	Stabilizing	0.984	D	0.845	deleterious	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.