TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28695	86308;86309;86310	chr2:178560049;178560048;178560047	chr2:179424776;179424775;179424774
N2AB	27054	81385;81386;81387	chr2:178560049;178560048;178560047	chr2:179424776;179424775;179424774
N2A	26127	78604;78605;78606	chr2:178560049;178560048;178560047	chr2:179424776;179424775;179424774
N2B	19630	59113;59114;59115	chr2:178560049;178560048;178560047	chr2:179424776;179424775;179424774
Novex-1	19755	59488;59489;59490	chr2:178560049;178560048;178560047	chr2:179424776;179424775;179424774
Novex-2	19822	59689;59690;59691	chr2:178560049;178560048;178560047	chr2:179424776;179424775;179424774
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-97
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.387
• 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/N	rs759939166	0.268	0.22	N	0.323	0.205	0.225902525712	gnomAD-2.1.1	2.83E-05	None	None	None	None	N	None	0	2.03122E-04	None	0	0	None	0	None	0	0	0
D/N	rs759939166	0.268	0.22	N	0.323	0.205	0.225902525712	gnomAD-4.0.0	6.15827E-06	None	None	None	None	N	None	0	1.78899E-04	None	0	0	None	0	0	8.99455E-07	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	0.1322	likely_benign	0.1226	benign	-0.248	Destabilizing	0.001	N	0.291	neutral	N	0.481941998	None	None	N
D/C	0.4446	ambiguous	0.4118	ambiguous	0.223	Stabilizing	0.909	D	0.565	neutral	None	None	None	None	N
D/E	0.0948	likely_benign	0.0892	benign	-0.399	Destabilizing	None	N	0.175	neutral	N	0.428664874	None	None	N
D/F	0.499	ambiguous	0.462	ambiguous	-0.418	Destabilizing	0.726	D	0.517	neutral	None	None	None	None	N
D/G	0.1295	likely_benign	0.1268	benign	-0.449	Destabilizing	0.124	N	0.275	neutral	N	0.460987936	None	None	N
D/H	0.2342	likely_benign	0.2237	benign	-0.524	Destabilizing	0.667	D	0.336	neutral	N	0.470492957	None	None	N
D/I	0.2648	likely_benign	0.2426	benign	0.232	Stabilizing	0.567	D	0.512	neutral	None	None	None	None	N
D/K	0.2523	likely_benign	0.2409	benign	0.244	Stabilizing	0.157	N	0.259	neutral	None	None	None	None	N
D/L	0.2917	likely_benign	0.2698	benign	0.232	Stabilizing	0.396	N	0.466	neutral	None	None	None	None	N
D/M	0.415	ambiguous	0.3878	ambiguous	0.55	Stabilizing	0.968	D	0.531	neutral	None	None	None	None	N
D/N	0.1032	likely_benign	0.0961	benign	0.097	Stabilizing	0.22	N	0.323	neutral	N	0.494100432	None	None	N
D/P	0.743	likely_pathogenic	0.7323	pathogenic	0.095	Stabilizing	0.726	D	0.327	neutral	None	None	None	None	N
D/Q	0.2057	likely_benign	0.1939	benign	0.101	Stabilizing	0.157	N	0.288	neutral	None	None	None	None	N
D/R	0.3011	likely_benign	0.2889	benign	0.265	Stabilizing	0.396	N	0.415	neutral	None	None	None	None	N
D/S	0.1052	likely_benign	0.1008	benign	-0.039	Destabilizing	0.157	N	0.282	neutral	None	None	None	None	N
D/T	0.1634	likely_benign	0.1507	benign	0.107	Stabilizing	0.272	N	0.315	neutral	None	None	None	None	N
D/V	0.1699	likely_benign	0.1537	benign	0.095	Stabilizing	0.124	N	0.463	neutral	N	0.505434934	None	None	N
D/W	0.8208	likely_pathogenic	0.8049	pathogenic	-0.372	Destabilizing	0.968	D	0.618	neutral	None	None	None	None	N
D/Y	0.2143	likely_benign	0.2003	benign	-0.204	Destabilizing	0.859	D	0.517	neutral	N	0.482609731	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.