TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28592	85999;86000;86001	chr2:178560358;178560357;178560356	chr2:179425085;179425084;179425083
N2AB	26951	81076;81077;81078	chr2:178560358;178560357;178560356	chr2:179425085;179425084;179425083
N2A	26024	78295;78296;78297	chr2:178560358;178560357;178560356	chr2:179425085;179425084;179425083
N2B	19527	58804;58805;58806	chr2:178560358;178560357;178560356	chr2:179425085;179425084;179425083
Novex-1	19652	59179;59180;59181	chr2:178560358;178560357;178560356	chr2:179425085;179425084;179425083
Novex-2	19719	59380;59381;59382	chr2:178560358;178560357;178560356	chr2:179425085;179425084;179425083
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: Fn3-96
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.3982
• 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	None	None	0.014	N	0.261	0.098	0.201204373187	gnomAD-4.0.0	4.77445E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.29898E-05	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	0.6658	likely_pathogenic	0.5992	pathogenic	-0.206	Destabilizing	0.86	D	0.541	neutral	None	None	None	None	N
K/C	0.895	likely_pathogenic	0.8473	pathogenic	-0.324	Destabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	N
K/D	0.9125	likely_pathogenic	0.8807	pathogenic	0.153	Stabilizing	0.915	D	0.549	neutral	None	None	None	None	N
K/E	0.4774	ambiguous	0.4079	ambiguous	0.191	Stabilizing	0.822	D	0.553	neutral	N	0.514574492	None	None	N
K/F	0.9535	likely_pathogenic	0.9306	pathogenic	-0.218	Destabilizing	0.998	D	0.699	prob.neutral	None	None	None	None	N
K/G	0.7147	likely_pathogenic	0.6732	pathogenic	-0.471	Destabilizing	0.754	D	0.62	neutral	None	None	None	None	N
K/H	0.6515	likely_pathogenic	0.5793	pathogenic	-0.776	Destabilizing	0.978	D	0.581	neutral	None	None	None	None	N
K/I	0.7153	likely_pathogenic	0.6257	pathogenic	0.432	Stabilizing	0.971	D	0.716	prob.delet.	N	0.47321889	None	None	N
K/L	0.6889	likely_pathogenic	0.6119	pathogenic	0.432	Stabilizing	0.956	D	0.615	neutral	None	None	None	None	N
K/M	0.4972	ambiguous	0.4236	ambiguous	0.265	Stabilizing	0.998	D	0.585	neutral	None	None	None	None	N
K/N	0.7898	likely_pathogenic	0.7245	pathogenic	0.075	Stabilizing	0.032	N	0.261	neutral	N	0.478093962	None	None	N
K/P	0.9205	likely_pathogenic	0.9008	pathogenic	0.249	Stabilizing	0.993	D	0.59	neutral	None	None	None	None	N
K/Q	0.2936	likely_benign	0.247	benign	-0.1	Destabilizing	0.942	D	0.567	neutral	N	0.508666931	None	None	N
K/R	0.1115	likely_benign	0.1001	benign	-0.195	Destabilizing	0.014	N	0.261	neutral	N	0.488660114	None	None	N
K/S	0.7813	likely_pathogenic	0.7184	pathogenic	-0.526	Destabilizing	0.754	D	0.529	neutral	None	None	None	None	N
K/T	0.5373	ambiguous	0.4552	ambiguous	-0.314	Destabilizing	0.822	D	0.556	neutral	N	0.466671523	None	None	N
K/V	0.6753	likely_pathogenic	0.5921	pathogenic	0.249	Stabilizing	0.978	D	0.685	prob.neutral	None	None	None	None	N
K/W	0.9279	likely_pathogenic	0.8986	pathogenic	-0.136	Destabilizing	0.998	D	0.688	prob.neutral	None	None	None	None	N
K/Y	0.8836	likely_pathogenic	0.843	pathogenic	0.185	Stabilizing	0.993	D	0.683	prob.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.