TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3277	10054;10055;10056	chr2:178764686;178764685;178764684	chr2:179629413;179629412;179629411
N2AB	3277	10054;10055;10056	chr2:178764686;178764685;178764684	chr2:179629413;179629412;179629411
N2A	3277	10054;10055;10056	chr2:178764686;178764685;178764684	chr2:179629413;179629412;179629411
N2B	3231	9916;9917;9918	chr2:178764686;178764685;178764684	chr2:179629413;179629412;179629411
Novex-1	3231	9916;9917;9918	chr2:178764686;178764685;178764684	chr2:179629413;179629412;179629411
Novex-2	3231	9916;9917;9918	chr2:178764686;178764685;178764684	chr2:179629413;179629412;179629411
Novex-3	3277	10054;10055;10056	chr2:178764686;178764685;178764684	chr2:179629413;179629412;179629411

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-23
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.529
• 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
Q/E	None	None	0.625	N	0.404	0.313	0.300784259202	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
Q/A	0.371	ambiguous	0.4357	ambiguous	-0.279	Destabilizing	0.525	D	0.387	neutral	None	None	None	None	N
Q/C	0.8319	likely_pathogenic	0.9082	pathogenic	0.01	Stabilizing	0.998	D	0.499	neutral	None	None	None	None	N
Q/D	0.6155	likely_pathogenic	0.6994	pathogenic	0.132	Stabilizing	0.842	D	0.368	neutral	None	None	None	None	N
Q/E	0.1333	likely_benign	0.1455	benign	0.167	Stabilizing	0.625	D	0.404	neutral	N	0.477922482	None	None	N
Q/F	0.8501	likely_pathogenic	0.9024	pathogenic	-0.254	Destabilizing	0.974	D	0.476	neutral	None	None	None	None	N
Q/G	0.4987	ambiguous	0.5989	pathogenic	-0.537	Destabilizing	0.842	D	0.424	neutral	None	None	None	None	N
Q/H	0.3565	ambiguous	0.4625	ambiguous	-0.259	Destabilizing	0.966	D	0.326	neutral	N	0.51589192	None	None	N
Q/I	0.5299	ambiguous	0.6174	pathogenic	0.331	Stabilizing	0.949	D	0.476	neutral	None	None	None	None	N
Q/K	0.1605	likely_benign	0.2062	benign	-0.026	Destabilizing	0.454	N	0.436	neutral	N	0.495149577	None	None	N
Q/L	0.2288	likely_benign	0.3004	benign	0.331	Stabilizing	0.669	D	0.417	neutral	N	0.508828003	None	None	N
Q/M	0.4717	ambiguous	0.5061	ambiguous	0.365	Stabilizing	0.991	D	0.327	neutral	None	None	None	None	N
Q/N	0.3709	ambiguous	0.4334	ambiguous	-0.538	Destabilizing	0.842	D	0.357	neutral	None	None	None	None	N
Q/P	0.7678	likely_pathogenic	0.9039	pathogenic	0.158	Stabilizing	0.966	D	0.351	neutral	D	0.637696358	None	None	N
Q/R	0.2026	likely_benign	0.2689	benign	0.101	Stabilizing	0.012	N	0.245	neutral	N	0.499980229	None	None	N
Q/S	0.4417	ambiguous	0.4944	ambiguous	-0.558	Destabilizing	0.728	D	0.379	neutral	None	None	None	None	N
Q/T	0.3109	likely_benign	0.3564	ambiguous	-0.347	Destabilizing	0.067	N	0.257	neutral	None	None	None	None	N
Q/V	0.3952	ambiguous	0.4558	ambiguous	0.158	Stabilizing	0.728	D	0.431	neutral	None	None	None	None	N
Q/W	0.8451	likely_pathogenic	0.9144	pathogenic	-0.219	Destabilizing	0.998	D	0.51	neutral	None	None	None	None	N
Q/Y	0.6708	likely_pathogenic	0.7718	pathogenic	0.033	Stabilizing	0.991	D	0.368	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.