TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31739	95440;95441;95442	chr2:178546021;178546020;178546019	chr2:179410748;179410747;179410746
N2AB	30098	90517;90518;90519	chr2:178546021;178546020;178546019	chr2:179410748;179410747;179410746
N2A	29171	87736;87737;87738	chr2:178546021;178546020;178546019	chr2:179410748;179410747;179410746
N2B	22674	68245;68246;68247	chr2:178546021;178546020;178546019	chr2:179410748;179410747;179410746
Novex-1	22799	68620;68621;68622	chr2:178546021;178546020;178546019	chr2:179410748;179410747;179410746
Novex-2	22866	68821;68822;68823	chr2:178546021;178546020;178546019	chr2:179410748;179410747;179410746
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-119
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.5863
• Predicted PPI site: I

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
E/D	None	None	0.024	N	0.272	0.025	0.110078149338	gnomAD-4.0.0	6.84219E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99475E-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
E/A	0.0833	likely_benign	0.0925	benign	-0.203	Destabilizing	None	N	0.132	neutral	N	0.466476688	None	None	I
E/C	0.6474	likely_pathogenic	0.7225	pathogenic	-0.032	Destabilizing	0.676	D	0.453	neutral	None	None	None	None	I
E/D	0.0898	likely_benign	0.0912	benign	-0.201	Destabilizing	0.024	N	0.272	neutral	N	0.457067771	None	None	I
E/F	0.6276	likely_pathogenic	0.7119	pathogenic	-0.135	Destabilizing	0.356	N	0.485	neutral	None	None	None	None	I
E/G	0.121	likely_benign	0.1467	benign	-0.379	Destabilizing	0.012	N	0.484	neutral	N	0.46707412	None	None	I
E/H	0.2873	likely_benign	0.3531	ambiguous	0.217	Stabilizing	0.001	N	0.199	neutral	None	None	None	None	I
E/I	0.2282	likely_benign	0.2901	benign	0.215	Stabilizing	0.001	N	0.339	neutral	None	None	None	None	I
E/K	0.0932	likely_benign	0.1159	benign	0.382	Stabilizing	0.012	N	0.267	neutral	N	0.439290086	None	None	I
E/L	0.2446	likely_benign	0.3019	benign	0.215	Stabilizing	0.016	N	0.515	neutral	None	None	None	None	I
E/M	0.2889	likely_benign	0.353	ambiguous	0.183	Stabilizing	0.356	N	0.467	neutral	None	None	None	None	I
E/N	0.144	likely_benign	0.1705	benign	0.14	Stabilizing	0.072	N	0.275	neutral	None	None	None	None	I
E/P	0.1737	likely_benign	0.1846	benign	0.096	Stabilizing	None	N	0.213	neutral	None	None	None	None	I
E/Q	0.0933	likely_benign	0.1082	benign	0.173	Stabilizing	0.001	N	0.177	neutral	N	0.512979768	None	None	I
E/R	0.1564	likely_benign	0.191	benign	0.603	Stabilizing	0.038	N	0.263	neutral	None	None	None	None	I
E/S	0.1168	likely_benign	0.1358	benign	-0.038	Destabilizing	0.003	N	0.151	neutral	None	None	None	None	I
E/T	0.1286	likely_benign	0.1586	benign	0.106	Stabilizing	0.001	N	0.221	neutral	None	None	None	None	I
E/V	0.1337	likely_benign	0.1626	benign	0.096	Stabilizing	0.012	N	0.493	neutral	N	0.479334956	None	None	I
E/W	0.7974	likely_pathogenic	0.8609	pathogenic	-0.028	Destabilizing	0.864	D	0.462	neutral	None	None	None	None	I
E/Y	0.477	ambiguous	0.5678	pathogenic	0.102	Stabilizing	0.214	N	0.473	neutral	None	None	None	None	I

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.