TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15903	47932;47933;47934	chr2:178617378;178617377;178617376	chr2:179482105;179482104;179482103
N2AB	14262	43009;43010;43011	chr2:178617378;178617377;178617376	chr2:179482105;179482104;179482103
N2A	13335	40228;40229;40230	chr2:178617378;178617377;178617376	chr2:179482105;179482104;179482103
N2B	6838	20737;20738;20739	chr2:178617378;178617377;178617376	chr2:179482105;179482104;179482103
Novex-1	6963	21112;21113;21114	chr2:178617378;178617377;178617376	chr2:179482105;179482104;179482103
Novex-2	7030	21313;21314;21315	chr2:178617378;178617377;178617376	chr2:179482105;179482104;179482103
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: Fn3-3
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.421
• 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	rs753276843	0.099	0.891	N	0.254	0.09	0.246215685461	gnomAD-2.1.1	1.85E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	4.03E-05	0
K/R	rs753276843	0.099	0.891	N	0.254	0.09	0.246215685461	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/R	rs753276843	0.099	0.891	N	0.254	0.09	0.246215685461	gnomAD-4.0.0	1.00779E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.28183E-05	0	1.62676E-05

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	0.246	likely_benign	0.2511	benign	0.047	Stabilizing	0.525	D	0.322	neutral	None	None	None	None	N
K/C	0.5657	likely_pathogenic	0.6075	pathogenic	0.015	Stabilizing	0.998	D	0.377	neutral	None	None	None	None	N
K/D	0.348	ambiguous	0.3576	ambiguous	-0.02	Destabilizing	0.842	D	0.259	neutral	None	None	None	None	N
K/E	0.1349	likely_benign	0.1312	benign	-0.022	Destabilizing	0.801	D	0.294	neutral	N	0.404605039	None	None	N
K/F	0.6808	likely_pathogenic	0.6981	pathogenic	-0.175	Destabilizing	0.974	D	0.365	neutral	None	None	None	None	N
K/G	0.2672	likely_benign	0.2592	benign	-0.153	Destabilizing	0.842	D	0.281	neutral	None	None	None	None	N
K/H	0.2669	likely_benign	0.3055	benign	-0.518	Destabilizing	0.991	D	0.301	neutral	None	None	None	None	N
K/I	0.3527	ambiguous	0.3543	ambiguous	0.497	Stabilizing	0.934	D	0.371	neutral	N	0.453680077	None	None	N
K/L	0.3169	likely_benign	0.3203	benign	0.497	Stabilizing	0.728	D	0.275	neutral	None	None	None	None	N
K/M	0.1851	likely_benign	0.1911	benign	0.368	Stabilizing	0.991	D	0.298	neutral	None	None	None	None	N
K/N	0.2046	likely_benign	0.2055	benign	0.38	Stabilizing	0.801	D	0.213	neutral	N	0.429983602	None	None	N
K/P	0.8108	likely_pathogenic	0.8297	pathogenic	0.375	Stabilizing	0.974	D	0.311	neutral	None	None	None	None	N
K/Q	0.1176	likely_benign	0.1273	benign	0.176	Stabilizing	0.966	D	0.299	neutral	N	0.448178496	None	None	N
K/R	0.0899	likely_benign	0.0963	benign	-0.012	Destabilizing	0.891	D	0.254	neutral	N	0.432986046	None	None	N
K/S	0.2037	likely_benign	0.2025	benign	-0.068	Destabilizing	0.172	N	0.149	neutral	None	None	None	None	N
K/T	0.1002	likely_benign	0.1007	benign	0.071	Stabilizing	0.007	N	0.115	neutral	N	0.336473789	None	None	N
K/V	0.2954	likely_benign	0.2934	benign	0.375	Stabilizing	0.728	D	0.291	neutral	None	None	None	None	N
K/W	0.7103	likely_pathogenic	0.7384	pathogenic	-0.199	Destabilizing	0.998	D	0.421	neutral	None	None	None	None	N
K/Y	0.555	ambiguous	0.5935	pathogenic	0.155	Stabilizing	0.991	D	0.337	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.