TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24996	75211;75212;75213	chr2:178571146;178571145;178571144	chr2:179435873;179435872;179435871
N2AB	23355	70288;70289;70290	chr2:178571146;178571145;178571144	chr2:179435873;179435872;179435871
N2A	22428	67507;67508;67509	chr2:178571146;178571145;178571144	chr2:179435873;179435872;179435871
N2B	15931	48016;48017;48018	chr2:178571146;178571145;178571144	chr2:179435873;179435872;179435871
Novex-1	16056	48391;48392;48393	chr2:178571146;178571145;178571144	chr2:179435873;179435872;179435871
Novex-2	16123	48592;48593;48594	chr2:178571146;178571145;178571144	chr2:179435873;179435872;179435871
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-69
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.5482
• 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
K/R	rs1206752183	None	0.012	N	0.533	0.078	0.247872288689	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.8226E-04	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
K/A	0.4946	ambiguous	0.5731	pathogenic	-0.01	Destabilizing	0.835	D	0.59	neutral	None	None	None	None	N
K/C	0.8129	likely_pathogenic	0.8602	pathogenic	-0.388	Destabilizing	0.998	D	0.775	deleterious	None	None	None	None	N
K/D	0.798	likely_pathogenic	0.8212	pathogenic	0.071	Stabilizing	0.899	D	0.631	neutral	None	None	None	None	N
K/E	0.4027	ambiguous	0.4791	ambiguous	0.066	Stabilizing	0.792	D	0.621	neutral	N	0.459406282	None	None	N
K/F	0.8924	likely_pathogenic	0.9216	pathogenic	-0.312	Destabilizing	0.998	D	0.749	deleterious	None	None	None	None	N
K/G	0.6303	likely_pathogenic	0.7095	pathogenic	-0.168	Destabilizing	0.717	D	0.595	neutral	None	None	None	None	N
K/H	0.4554	ambiguous	0.5011	ambiguous	-0.363	Destabilizing	0.973	D	0.635	neutral	None	None	None	None	N
K/I	0.5999	likely_pathogenic	0.6608	pathogenic	0.318	Stabilizing	0.964	D	0.765	deleterious	N	0.469452546	None	None	N
K/L	0.5367	ambiguous	0.6032	pathogenic	0.318	Stabilizing	0.947	D	0.597	neutral	None	None	None	None	N
K/M	0.4474	ambiguous	0.5182	ambiguous	0.085	Stabilizing	0.998	D	0.621	neutral	None	None	None	None	N
K/N	0.6933	likely_pathogenic	0.742	pathogenic	0.095	Stabilizing	0.027	N	0.459	neutral	N	0.461993353	None	None	N
K/P	0.6587	likely_pathogenic	0.7024	pathogenic	0.235	Stabilizing	0.991	D	0.63	neutral	None	None	None	None	N
K/Q	0.2536	likely_benign	0.3074	benign	-0.065	Destabilizing	0.931	D	0.643	neutral	N	0.495311154	None	None	N
K/R	0.0842	likely_benign	0.0909	benign	-0.056	Destabilizing	0.012	N	0.533	neutral	N	0.478592262	None	None	N
K/S	0.6477	likely_pathogenic	0.7114	pathogenic	-0.379	Destabilizing	0.717	D	0.553	neutral	None	None	None	None	N
K/T	0.4093	ambiguous	0.4789	ambiguous	-0.247	Destabilizing	0.792	D	0.641	neutral	N	0.501506407	None	None	N
K/V	0.5133	ambiguous	0.5784	pathogenic	0.235	Stabilizing	0.973	D	0.708	prob.delet.	None	None	None	None	N
K/W	0.8652	likely_pathogenic	0.8987	pathogenic	-0.351	Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
K/Y	0.7802	likely_pathogenic	0.8166	pathogenic	0.013	Stabilizing	0.991	D	0.754	deleterious	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.