TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2178	6757;6758;6759	chr2:178775179;178775178;178775177	chr2:179639906;179639905;179639904
N2AB	2178	6757;6758;6759	chr2:178775179;178775178;178775177	chr2:179639906;179639905;179639904
N2A	2178	6757;6758;6759	chr2:178775179;178775178;178775177	chr2:179639906;179639905;179639904
N2B	2132	6619;6620;6621	chr2:178775179;178775178;178775177	chr2:179639906;179639905;179639904
Novex-1	2132	6619;6620;6621	chr2:178775179;178775178;178775177	chr2:179639906;179639905;179639904
Novex-2	2132	6619;6620;6621	chr2:178775179;178775178;178775177	chr2:179639906;179639905;179639904
Novex-3	2178	6757;6758;6759	chr2:178775179;178775178;178775177	chr2:179639906;179639905;179639904

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-11
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.4955
• 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/R	None	None	0.77	N	0.536	0.4	0.253205268125	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	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
Q/A	0.323	likely_benign	0.3349	benign	-0.536	Destabilizing	0.816	D	0.549	neutral	None	None	None	None	N
Q/C	0.8479	likely_pathogenic	0.8629	pathogenic	0.084	Stabilizing	0.997	D	0.685	prob.neutral	None	None	None	None	N
Q/D	0.5991	likely_pathogenic	0.6257	pathogenic	-0.685	Destabilizing	0.69	D	0.518	neutral	None	None	None	None	N
Q/E	0.1184	likely_benign	0.1237	benign	-0.608	Destabilizing	0.004	N	0.109	neutral	N	0.510461847	None	None	N
Q/F	0.8889	likely_pathogenic	0.9014	pathogenic	-0.229	Destabilizing	0.99	D	0.636	neutral	None	None	None	None	N
Q/G	0.4	ambiguous	0.4189	ambiguous	-0.885	Destabilizing	0.9	D	0.529	neutral	None	None	None	None	N
Q/H	0.3204	likely_benign	0.34	benign	-0.786	Destabilizing	0.96	D	0.548	neutral	N	0.512078076	None	None	N
Q/I	0.6075	likely_pathogenic	0.6309	pathogenic	0.348	Stabilizing	0.969	D	0.623	neutral	None	None	None	None	N
Q/K	0.1022	likely_benign	0.1075	benign	-0.424	Destabilizing	0.409	N	0.55	neutral	N	0.46212684	None	None	N
Q/L	0.2664	likely_benign	0.2818	benign	0.348	Stabilizing	0.77	D	0.499	neutral	D	0.557225818	None	None	N
Q/M	0.5186	ambiguous	0.5338	ambiguous	0.811	Stabilizing	0.99	D	0.547	neutral	None	None	None	None	N
Q/N	0.4275	ambiguous	0.4434	ambiguous	-0.886	Destabilizing	0.816	D	0.491	neutral	None	None	None	None	N
Q/P	0.84	likely_pathogenic	0.8613	pathogenic	0.085	Stabilizing	0.96	D	0.539	neutral	D	0.640255698	None	None	N
Q/R	0.1268	likely_benign	0.1347	benign	-0.319	Destabilizing	0.77	D	0.536	neutral	N	0.493540231	None	None	N
Q/S	0.3712	ambiguous	0.3832	ambiguous	-0.942	Destabilizing	0.816	D	0.513	neutral	None	None	None	None	N
Q/T	0.2831	likely_benign	0.2918	benign	-0.682	Destabilizing	0.816	D	0.523	neutral	None	None	None	None	N
Q/V	0.3965	ambiguous	0.4168	ambiguous	0.085	Stabilizing	0.969	D	0.487	neutral	None	None	None	None	N
Q/W	0.7927	likely_pathogenic	0.8224	pathogenic	-0.145	Destabilizing	0.997	D	0.691	prob.neutral	None	None	None	None	N
Q/Y	0.7077	likely_pathogenic	0.7333	pathogenic	0.068	Stabilizing	0.99	D	0.605	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.