TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19846	59761;59762;59763	chr2:178592469;178592468;178592467	chr2:179457196;179457195;179457194
N2AB	18205	54838;54839;54840	chr2:178592469;178592468;178592467	chr2:179457196;179457195;179457194
N2A	17278	52057;52058;52059	chr2:178592469;178592468;178592467	chr2:179457196;179457195;179457194
N2B	10781	32566;32567;32568	chr2:178592469;178592468;178592467	chr2:179457196;179457195;179457194
Novex-1	10906	32941;32942;32943	chr2:178592469;178592468;178592467	chr2:179457196;179457195;179457194
Novex-2	10973	33142;33143;33144	chr2:178592469;178592468;178592467	chr2:179457196;179457195;179457194
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-119
• Domain position: 57
• Structural Position: 143
• Q(SASA): 0.681
• 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
N/H	rs749738999	-0.614	0.976	N	0.339	0.252	0.194818534648	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
N/H	rs749738999	-0.614	0.976	N	0.339	0.252	0.194818534648	gnomAD-4.0.0	3.18366E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71873E-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
N/A	0.278	likely_benign	0.2491	benign	-0.35	Destabilizing	0.863	D	0.357	neutral	None	None	None	None	N
N/C	0.3575	ambiguous	0.3252	benign	0.431	Stabilizing	0.999	D	0.363	neutral	None	None	None	None	N
N/D	0.1057	likely_benign	0.1046	benign	-0.072	Destabilizing	0.852	D	0.287	neutral	N	0.46290516	None	None	N
N/E	0.2953	likely_benign	0.2936	benign	-0.116	Destabilizing	0.17	N	0.187	neutral	None	None	None	None	N
N/F	0.5605	ambiguous	0.5125	ambiguous	-0.754	Destabilizing	0.02	N	0.213	neutral	None	None	None	None	N
N/G	0.2483	likely_benign	0.2267	benign	-0.515	Destabilizing	0.927	D	0.257	neutral	None	None	None	None	N
N/H	0.1233	likely_benign	0.1169	benign	-0.618	Destabilizing	0.976	D	0.339	neutral	N	0.498097956	None	None	N
N/I	0.4414	ambiguous	0.4138	ambiguous	-0.005	Destabilizing	0.92	D	0.421	neutral	N	0.464066814	None	None	N
N/K	0.3081	likely_benign	0.2954	benign	0.14	Stabilizing	0.92	D	0.255	neutral	N	0.438817579	None	None	N
N/L	0.344	ambiguous	0.3233	benign	-0.005	Destabilizing	0.884	D	0.403	neutral	None	None	None	None	N
N/M	0.4103	ambiguous	0.3718	ambiguous	0.496	Stabilizing	0.997	D	0.353	neutral	None	None	None	None	N
N/P	0.742	likely_pathogenic	0.7389	pathogenic	-0.094	Destabilizing	0.997	D	0.384	neutral	None	None	None	None	N
N/Q	0.3064	likely_benign	0.2906	benign	-0.355	Destabilizing	0.982	D	0.316	neutral	None	None	None	None	N
N/R	0.3685	ambiguous	0.3612	ambiguous	0.226	Stabilizing	0.939	D	0.33	neutral	None	None	None	None	N
N/S	0.1134	likely_benign	0.1067	benign	-0.062	Destabilizing	0.826	D	0.294	neutral	N	0.465580106	None	None	N
N/T	0.2146	likely_benign	0.2007	benign	0.03	Stabilizing	0.959	D	0.263	neutral	N	0.498097956	None	None	N
N/V	0.3881	ambiguous	0.3627	ambiguous	-0.094	Destabilizing	0.939	D	0.401	neutral	None	None	None	None	N
N/W	0.7499	likely_pathogenic	0.7296	pathogenic	-0.726	Destabilizing	0.998	D	0.358	neutral	None	None	None	None	N
N/Y	0.1817	likely_benign	0.1667	benign	-0.458	Destabilizing	0.134	N	0.197	neutral	N	0.490094548	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.