TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23966	72121;72122;72123	chr2:178574236;178574235;178574234	chr2:179438963;179438962;179438961
N2AB	22325	67198;67199;67200	chr2:178574236;178574235;178574234	chr2:179438963;179438962;179438961
N2A	21398	64417;64418;64419	chr2:178574236;178574235;178574234	chr2:179438963;179438962;179438961
N2B	14901	44926;44927;44928	chr2:178574236;178574235;178574234	chr2:179438963;179438962;179438961
Novex-1	15026	45301;45302;45303	chr2:178574236;178574235;178574234	chr2:179438963;179438962;179438961
Novex-2	15093	45502;45503;45504	chr2:178574236;178574235;178574234	chr2:179438963;179438962;179438961
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-62
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.2146
• 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
L/P	None	None	0.99	N	0.736	0.512	0.773781150904	gnomAD-4.0.0	1.59242E-06	None	None	None	None	N	None	0	0	None	0	2.78319E-05	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
L/A	0.5589	ambiguous	0.5883	pathogenic	-1.753	Destabilizing	0.86	D	0.555	neutral	None	None	None	None	N
L/C	0.722	likely_pathogenic	0.7632	pathogenic	-0.865	Destabilizing	0.998	D	0.625	neutral	None	None	None	None	N
L/D	0.9399	likely_pathogenic	0.9472	pathogenic	-1.305	Destabilizing	0.993	D	0.742	deleterious	None	None	None	None	N
L/E	0.7562	likely_pathogenic	0.7968	pathogenic	-1.34	Destabilizing	0.993	D	0.746	deleterious	None	None	None	None	N
L/F	0.3429	ambiguous	0.3644	ambiguous	-1.395	Destabilizing	0.032	N	0.274	neutral	N	0.485802963	None	None	N
L/G	0.8231	likely_pathogenic	0.8369	pathogenic	-2.042	Highly Destabilizing	0.978	D	0.746	deleterious	None	None	None	None	N
L/H	0.5116	ambiguous	0.5641	pathogenic	-1.252	Destabilizing	0.997	D	0.719	prob.delet.	N	0.467191729	None	None	N
L/I	0.1058	likely_benign	0.1178	benign	-1.038	Destabilizing	0.698	D	0.507	neutral	N	0.50280006	None	None	N
L/K	0.5234	ambiguous	0.5669	pathogenic	-1.123	Destabilizing	0.978	D	0.711	prob.delet.	None	None	None	None	N
L/M	0.1963	likely_benign	0.207	benign	-0.666	Destabilizing	0.356	N	0.209	neutral	None	None	None	None	N
L/N	0.6912	likely_pathogenic	0.7051	pathogenic	-0.826	Destabilizing	0.993	D	0.739	prob.delet.	None	None	None	None	N
L/P	0.8944	likely_pathogenic	0.8972	pathogenic	-1.246	Destabilizing	0.99	D	0.736	prob.delet.	N	0.504050854	None	None	N
L/Q	0.4159	ambiguous	0.4557	ambiguous	-1.093	Destabilizing	0.978	D	0.712	prob.delet.	None	None	None	None	N
L/R	0.439	ambiguous	0.5058	ambiguous	-0.441	Destabilizing	0.971	D	0.705	prob.neutral	N	0.469064607	None	None	N
L/S	0.6342	likely_pathogenic	0.6709	pathogenic	-1.384	Destabilizing	0.978	D	0.688	prob.neutral	None	None	None	None	N
L/T	0.5101	ambiguous	0.5436	ambiguous	-1.315	Destabilizing	0.978	D	0.583	neutral	None	None	None	None	N
L/V	0.1426	likely_benign	0.1559	benign	-1.246	Destabilizing	0.698	D	0.524	neutral	N	0.454910113	None	None	N
L/W	0.6356	likely_pathogenic	0.6802	pathogenic	-1.42	Destabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	N
L/Y	0.5946	likely_pathogenic	0.6355	pathogenic	-1.228	Destabilizing	0.915	D	0.632	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.