TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17244	51955;51956;51957	chr2:178609693;178609692;178609691	chr2:179474420;179474419;179474418
N2AB	15603	47032;47033;47034	chr2:178609693;178609692;178609691	chr2:179474420;179474419;179474418
N2A	14676	44251;44252;44253	chr2:178609693;178609692;178609691	chr2:179474420;179474419;179474418
N2B	8179	24760;24761;24762	chr2:178609693;178609692;178609691	chr2:179474420;179474419;179474418
Novex-1	8304	25135;25136;25137	chr2:178609693;178609692;178609691	chr2:179474420;179474419;179474418
Novex-2	8371	25336;25337;25338	chr2:178609693;178609692;178609691	chr2:179474420;179474419;179474418
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-13
• Domain position: 98
• Structural Position: 132
• Q(SASA): 1.0335
• 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/E	None	None	0.999	N	0.527	0.156	0.257292322809	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	5.25001E-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
D/A	0.4462	ambiguous	0.4539	ambiguous	-0.098	Destabilizing	1.0	D	0.76	deleterious	N	0.486769193	None	None	N
D/C	0.9078	likely_pathogenic	0.9015	pathogenic	0.036	Stabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
D/E	0.5301	ambiguous	0.5391	ambiguous	-0.247	Destabilizing	0.999	D	0.527	neutral	N	0.499058827	None	None	N
D/F	0.8783	likely_pathogenic	0.8726	pathogenic	-0.153	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
D/G	0.6683	likely_pathogenic	0.6707	pathogenic	-0.252	Destabilizing	1.0	D	0.801	deleterious	N	0.510153367	None	None	N
D/H	0.6756	likely_pathogenic	0.6811	pathogenic	0.169	Stabilizing	1.0	D	0.895	deleterious	N	0.510913836	None	None	N
D/I	0.8269	likely_pathogenic	0.8279	pathogenic	0.247	Stabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
D/K	0.8356	likely_pathogenic	0.8371	pathogenic	0.405	Stabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
D/L	0.6875	likely_pathogenic	0.6664	pathogenic	0.247	Stabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
D/M	0.9133	likely_pathogenic	0.9166	pathogenic	0.229	Stabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
D/N	0.2027	likely_benign	0.2186	benign	0.183	Stabilizing	1.0	D	0.797	deleterious	N	0.496897731	None	None	N
D/P	0.7845	likely_pathogenic	0.7794	pathogenic	0.153	Stabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
D/Q	0.8164	likely_pathogenic	0.817	pathogenic	0.199	Stabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
D/R	0.8767	likely_pathogenic	0.8795	pathogenic	0.568	Stabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
D/S	0.303	likely_benign	0.3146	benign	0.085	Stabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
D/T	0.6977	likely_pathogenic	0.7069	pathogenic	0.204	Stabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
D/V	0.6794	likely_pathogenic	0.6855	pathogenic	0.153	Stabilizing	1.0	D	0.809	deleterious	N	0.51778669	None	None	N
D/W	0.9784	likely_pathogenic	0.9769	pathogenic	-0.086	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
D/Y	0.5693	likely_pathogenic	0.5438	ambiguous	0.071	Stabilizing	1.0	D	0.847	deleterious	D	0.537665371	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.