TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7001	21226;21227;21228	chr2:178724374;178724373;178724372	chr2:179589101;179589100;179589099
N2AB	6684	20275;20276;20277	chr2:178724374;178724373;178724372	chr2:179589101;179589100;179589099
N2A	5757	17494;17495;17496	chr2:178724374;178724373;178724372	chr2:179589101;179589100;179589099
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-54
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.3876
• 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	rs200594798	-0.198	0.642	N	0.336	0.108	None	gnomAD-2.1.1	2.46363E-04	None	None	None	None	N	None	2.77043E-03	5.66E-05	None	0	0	None	0	None	0	0	0
K/R	rs200594798	-0.198	0.642	N	0.336	0.108	None	gnomAD-3.1.2	6.44152E-04	None	None	None	None	N	None	2.31649E-03	1.31044E-04	0	0	0	None	0	0	0	0	0
K/R	rs200594798	-0.198	0.642	N	0.336	0.108	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
K/R	rs200594798	-0.198	0.642	N	0.336	0.108	None	gnomAD-4.0.0	1.33867E-04	None	None	None	None	N	None	2.69312E-03	1.16709E-04	None	0	0	None	0	0	8.47744E-07	0	9.60707E-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	0.4382	ambiguous	0.4779	ambiguous	-0.59	Destabilizing	0.329	N	0.403	neutral	None	None	None	None	N
K/C	0.7414	likely_pathogenic	0.7768	pathogenic	-0.686	Destabilizing	0.995	D	0.506	neutral	None	None	None	None	N
K/D	0.4369	ambiguous	0.4756	ambiguous	0.014	Stabilizing	0.543	D	0.391	neutral	None	None	None	None	N
K/E	0.1877	likely_benign	0.2161	benign	0.167	Stabilizing	0.425	N	0.337	neutral	N	0.437319722	None	None	N
K/F	0.8275	likely_pathogenic	0.8508	pathogenic	-0.226	Destabilizing	0.893	D	0.539	neutral	None	None	None	None	N
K/G	0.3055	likely_benign	0.3282	benign	-0.962	Destabilizing	0.329	N	0.457	neutral	None	None	None	None	N
K/H	0.2633	likely_benign	0.2816	benign	-1.049	Destabilizing	0.944	D	0.489	neutral	None	None	None	None	N
K/I	0.6571	likely_pathogenic	0.6854	pathogenic	0.382	Stabilizing	0.473	N	0.527	neutral	N	0.485999103	None	None	N
K/L	0.486	ambiguous	0.5176	ambiguous	0.382	Stabilizing	0.329	N	0.457	neutral	None	None	None	None	N
K/M	0.2708	likely_benign	0.2926	benign	-0.007	Destabilizing	0.176	N	0.313	neutral	None	None	None	None	N
K/N	0.2538	likely_benign	0.2703	benign	-0.546	Destabilizing	0.002	N	0.142	neutral	N	0.432375262	None	None	N
K/P	0.8892	likely_pathogenic	0.9188	pathogenic	0.087	Stabilizing	0.944	D	0.495	neutral	None	None	None	None	N
K/Q	0.1156	likely_benign	0.1249	benign	-0.464	Destabilizing	0.784	D	0.44	neutral	N	0.435050208	None	None	N
K/R	0.0827	likely_benign	0.0867	benign	-0.414	Destabilizing	0.642	D	0.336	neutral	N	0.43853323	None	None	N
K/S	0.3644	ambiguous	0.4045	ambiguous	-1.186	Destabilizing	0.085	N	0.141	neutral	None	None	None	None	N
K/T	0.2337	likely_benign	0.2734	benign	-0.811	Destabilizing	0.023	N	0.205	neutral	N	0.446883354	None	None	N
K/V	0.5893	likely_pathogenic	0.6252	pathogenic	0.087	Stabilizing	0.543	D	0.448	neutral	None	None	None	None	N
K/W	0.7864	likely_pathogenic	0.8265	pathogenic	-0.159	Destabilizing	0.995	D	0.547	neutral	None	None	None	None	N
K/Y	0.5838	likely_pathogenic	0.6232	pathogenic	0.14	Stabilizing	0.981	D	0.519	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.