TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23911	71956;71957;71958	chr2:178574401;178574400;178574399	chr2:179439128;179439127;179439126
N2AB	22270	67033;67034;67035	chr2:178574401;178574400;178574399	chr2:179439128;179439127;179439126
N2A	21343	64252;64253;64254	chr2:178574401;178574400;178574399	chr2:179439128;179439127;179439126
N2B	14846	44761;44762;44763	chr2:178574401;178574400;178574399	chr2:179439128;179439127;179439126
Novex-1	14971	45136;45137;45138	chr2:178574401;178574400;178574399	chr2:179439128;179439127;179439126
Novex-2	15038	45337;45338;45339	chr2:178574401;178574400;178574399	chr2:179439128;179439127;179439126
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: Fn3-61
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.521
• Predicted PPI site: I

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/E	rs763131148	0.441	0.977	N	0.627	0.281	0.317667799068	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
K/E	rs763131148	0.441	0.977	N	0.627	0.281	0.317667799068	gnomAD-3.1.2	3.29E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	7.35E-05	0	0
K/E	rs763131148	0.441	0.977	N	0.627	0.281	0.317667799068	gnomAD-4.0.0	3.03697E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.98429E-05	0	3.20277E-05
K/Q	None	None	0.993	N	0.726	0.306	0.229924730088	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/Q	None	None	0.993	N	0.726	0.306	0.229924730088	gnomAD-4.0.0	6.57307E-06	None	None	None	None	I	None	2.41266E-05	0	None	0	0	None	0	0	0	0	0
K/R	rs570788965	0.005	0.235	N	0.327	0.149	0.21737058555	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	0	0	0	0	3.86847E-04	None	0	0	0	0	0
K/R	rs570788965	0.005	0.235	N	0.327	0.149	0.21737058555	1000 genomes	3.99361E-04	None	None	None	None	I	None	0	0	None	None	2E-03	0	None	None	None	0	None
K/R	rs570788965	0.005	0.235	N	0.327	0.149	0.21737058555	gnomAD-4.0.0	3.84378E-06	None	None	None	None	I	None	0	0	None	0	7.27979E-05	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	0.4793	ambiguous	0.5081	ambiguous	0.006	Stabilizing	0.983	D	0.664	neutral	None	None	None	None	I
K/C	0.785	likely_pathogenic	0.7955	pathogenic	-0.298	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	I
K/D	0.7939	likely_pathogenic	0.8038	pathogenic	0.001	Stabilizing	0.998	D	0.751	deleterious	None	None	None	None	I
K/E	0.3999	ambiguous	0.429	ambiguous	0.013	Stabilizing	0.977	D	0.627	neutral	N	0.441980888	None	None	I
K/F	0.8415	likely_pathogenic	0.8628	pathogenic	-0.208	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	I
K/G	0.6406	likely_pathogenic	0.6544	pathogenic	-0.186	Destabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	I
K/H	0.4626	ambiguous	0.471	ambiguous	-0.388	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	I
K/I	0.4319	ambiguous	0.5025	ambiguous	0.431	Stabilizing	0.998	D	0.733	prob.delet.	None	None	None	None	I
K/L	0.4312	ambiguous	0.479	ambiguous	0.431	Stabilizing	0.995	D	0.685	prob.neutral	None	None	None	None	I
K/M	0.3706	ambiguous	0.412	ambiguous	0.098	Stabilizing	1.0	D	0.688	prob.neutral	N	0.481510549	None	None	I
K/N	0.656	likely_pathogenic	0.6933	pathogenic	0.123	Stabilizing	0.993	D	0.727	prob.delet.	N	0.474420204	None	None	I
K/P	0.5333	ambiguous	0.5582	ambiguous	0.316	Stabilizing	0.999	D	0.74	deleterious	None	None	None	None	I
K/Q	0.2169	likely_benign	0.2296	benign	-0.006	Destabilizing	0.993	D	0.726	prob.delet.	N	0.510899468	None	None	I
K/R	0.1004	likely_benign	0.098	benign	-0.065	Destabilizing	0.235	N	0.327	neutral	N	0.481000636	None	None	I
K/S	0.5881	likely_pathogenic	0.6261	pathogenic	-0.323	Destabilizing	0.983	D	0.693	prob.neutral	None	None	None	None	I
K/T	0.354	ambiguous	0.3984	ambiguous	-0.163	Destabilizing	0.997	D	0.722	prob.delet.	N	0.469393775	None	None	I
K/V	0.4143	ambiguous	0.4731	ambiguous	0.316	Stabilizing	0.998	D	0.739	prob.delet.	None	None	None	None	I
K/W	0.8806	likely_pathogenic	0.8713	pathogenic	-0.26	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
K/Y	0.7403	likely_pathogenic	0.7458	pathogenic	0.095	Stabilizing	0.999	D	0.745	deleterious	None	None	None	None	I

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.