TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28514	85765;85766;85767	chr2:178560592;178560591;178560590	chr2:179425319;179425318;179425317
N2AB	26873	80842;80843;80844	chr2:178560592;178560591;178560590	chr2:179425319;179425318;179425317
N2A	25946	78061;78062;78063	chr2:178560592;178560591;178560590	chr2:179425319;179425318;179425317
N2B	19449	58570;58571;58572	chr2:178560592;178560591;178560590	chr2:179425319;179425318;179425317
Novex-1	19574	58945;58946;58947	chr2:178560592;178560591;178560590	chr2:179425319;179425318;179425317
Novex-2	19641	59146;59147;59148	chr2:178560592;178560591;178560590	chr2:179425319;179425318;179425317
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-95
• Domain position: 65
• Structural Position: 96
• Q(SASA): 0.8587
• 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/N	None	None	0.967	N	0.492	0.204	0.159798565429	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
K/Q	rs1401382571	0.248	0.967	N	0.561	0.317	0.221734844693	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	5.61E-05	None	0	None	0	0	0
K/Q	rs1401382571	0.248	0.967	N	0.561	0.317	0.221734844693	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.93199E-04	None	0	0	0	0	0
K/Q	rs1401382571	0.248	0.967	N	0.561	0.317	0.221734844693	gnomAD-4.0.0	6.57134E-06	None	None	None	None	N	None	0	0	None	0	1.93199E-04	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
K/A	0.521	ambiguous	0.6424	pathogenic	0.094	Stabilizing	0.916	D	0.501	neutral	None	None	None	None	N
K/C	0.7442	likely_pathogenic	0.8395	pathogenic	-0.309	Destabilizing	0.999	D	0.666	neutral	None	None	None	None	N
K/D	0.6462	likely_pathogenic	0.7607	pathogenic	-0.112	Destabilizing	0.975	D	0.509	neutral	None	None	None	None	N
K/E	0.4018	ambiguous	0.5191	ambiguous	-0.109	Destabilizing	0.892	D	0.522	neutral	N	0.468139554	None	None	N
K/F	0.92	likely_pathogenic	0.9507	pathogenic	-0.143	Destabilizing	0.987	D	0.624	neutral	None	None	None	None	N
K/G	0.3709	ambiguous	0.4924	ambiguous	-0.075	Destabilizing	0.916	D	0.475	neutral	None	None	None	None	N
K/H	0.324	likely_benign	0.3992	ambiguous	-0.186	Destabilizing	0.073	N	0.44	neutral	None	None	None	None	N
K/I	0.8259	likely_pathogenic	0.8824	pathogenic	0.46	Stabilizing	0.987	D	0.623	neutral	None	None	None	None	N
K/L	0.6587	likely_pathogenic	0.746	pathogenic	0.46	Stabilizing	0.975	D	0.463	neutral	None	None	None	None	N
K/M	0.5475	ambiguous	0.646	pathogenic	0.064	Stabilizing	0.999	D	0.51	neutral	N	0.507198901	None	None	N
K/N	0.4951	ambiguous	0.6004	pathogenic	0.136	Stabilizing	0.967	D	0.492	neutral	N	0.476765465	None	None	N
K/P	0.8427	likely_pathogenic	0.8956	pathogenic	0.364	Stabilizing	0.996	D	0.52	neutral	None	None	None	None	N
K/Q	0.231	likely_benign	0.2873	benign	0.001	Stabilizing	0.967	D	0.561	neutral	N	0.494828637	None	None	N
K/R	0.0833	likely_benign	0.0893	benign	-0.011	Destabilizing	0.025	N	0.273	neutral	N	0.470554356	None	None	N
K/S	0.506	ambiguous	0.6285	pathogenic	-0.265	Destabilizing	0.916	D	0.509	neutral	None	None	None	None	N
K/T	0.431	ambiguous	0.5503	ambiguous	-0.13	Destabilizing	0.967	D	0.505	neutral	N	0.495335616	None	None	N
K/V	0.703	likely_pathogenic	0.784	pathogenic	0.364	Stabilizing	0.987	D	0.543	neutral	None	None	None	None	N
K/W	0.8539	likely_pathogenic	0.8985	pathogenic	-0.226	Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	N
K/Y	0.748	likely_pathogenic	0.8204	pathogenic	0.13	Stabilizing	0.95	D	0.56	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.