TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22101	66526;66527;66528	chr2:178582068;178582067;178582066	chr2:179446795;179446794;179446793
N2AB	20460	61603;61604;61605	chr2:178582068;178582067;178582066	chr2:179446795;179446794;179446793
N2A	19533	58822;58823;58824	chr2:178582068;178582067;178582066	chr2:179446795;179446794;179446793
N2B	13036	39331;39332;39333	chr2:178582068;178582067;178582066	chr2:179446795;179446794;179446793
Novex-1	13161	39706;39707;39708	chr2:178582068;178582067;178582066	chr2:179446795;179446794;179446793
Novex-2	13228	39907;39908;39909	chr2:178582068;178582067;178582066	chr2:179446795;179446794;179446793
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-48
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.6995
• 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
N/Y	None	None	0.954	N	0.304	0.33	0.519514513453	gnomAD-4.0.0	2.05314E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69899E-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	0.212	likely_benign	0.2318	benign	-0.121	Destabilizing	0.002	N	0.18	neutral	None	None	None	None	I
N/C	0.2643	likely_benign	0.2757	benign	0.184	Stabilizing	0.991	D	0.291	neutral	None	None	None	None	I
N/D	0.3446	ambiguous	0.3563	ambiguous	0.217	Stabilizing	0.491	N	0.281	neutral	N	0.437863147	None	None	I
N/E	0.5935	likely_pathogenic	0.6206	pathogenic	0.175	Stabilizing	0.345	N	0.247	neutral	None	None	None	None	I
N/F	0.4887	ambiguous	0.4893	ambiguous	-0.669	Destabilizing	0.965	D	0.314	neutral	None	None	None	None	I
N/G	0.276	likely_benign	0.2946	benign	-0.243	Destabilizing	0.209	N	0.257	neutral	None	None	None	None	I
N/H	0.1283	likely_benign	0.1235	benign	-0.24	Destabilizing	0.873	D	0.262	neutral	N	0.478288405	None	None	I
N/I	0.1935	likely_benign	0.2065	benign	0.104	Stabilizing	0.772	D	0.345	neutral	N	0.497220882	None	None	I
N/K	0.4781	ambiguous	0.5223	ambiguous	0.113	Stabilizing	0.166	N	0.265	neutral	N	0.444213117	None	None	I
N/L	0.2162	likely_benign	0.2221	benign	0.104	Stabilizing	0.561	D	0.313	neutral	None	None	None	None	I
N/M	0.3131	likely_benign	0.3236	benign	0.045	Stabilizing	0.965	D	0.3	neutral	None	None	None	None	I
N/P	0.6531	likely_pathogenic	0.6685	pathogenic	0.053	Stabilizing	0.722	D	0.351	neutral	None	None	None	None	I
N/Q	0.3663	ambiguous	0.3902	ambiguous	-0.16	Destabilizing	0.561	D	0.237	neutral	None	None	None	None	I
N/R	0.4832	ambiguous	0.5083	ambiguous	0.163	Stabilizing	0.004	N	0.219	neutral	None	None	None	None	I
N/S	0.0909	likely_benign	0.0946	benign	0.002	Stabilizing	0.005	N	0.085	neutral	N	0.453235245	None	None	I
N/T	0.1174	likely_benign	0.1258	benign	0.081	Stabilizing	0.005	N	0.097	neutral	N	0.423896559	None	None	I
N/V	0.2016	likely_benign	0.2149	benign	0.053	Stabilizing	0.39	N	0.317	neutral	None	None	None	None	I
N/W	0.7795	likely_pathogenic	0.7697	pathogenic	-0.798	Destabilizing	0.991	D	0.323	neutral	None	None	None	None	I
N/Y	0.1774	likely_benign	0.1689	benign	-0.471	Destabilizing	0.954	D	0.304	neutral	N	0.500895906	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.