TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30084	90475;90476;90477	chr2:178552650;178552649;178552648	chr2:179417377;179417376;179417375
N2AB	28443	85552;85553;85554	chr2:178552650;178552649;178552648	chr2:179417377;179417376;179417375
N2A	27516	82771;82772;82773	chr2:178552650;178552649;178552648	chr2:179417377;179417376;179417375
N2B	21019	63280;63281;63282	chr2:178552650;178552649;178552648	chr2:179417377;179417376;179417375
Novex-1	21144	63655;63656;63657	chr2:178552650;178552649;178552648	chr2:179417377;179417376;179417375
Novex-2	21211	63856;63857;63858	chr2:178552650;178552649;178552648	chr2:179417377;179417376;179417375
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: Fn3-107
• Domain position: 55
• Structural Position: 83
• Q(SASA): 0.8525
• 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/E	rs376597164	0.404	0.992	N	0.598	0.333	0.343334270461	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	0	0	None	0	2.78707E-04	None	0	None	0	0	0
K/E	rs376597164	0.404	0.992	N	0.598	0.333	0.343334270461	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92753E-04	None	0	0	0	0	0
K/E	rs376597164	0.404	0.992	N	0.598	0.333	0.343334270461	gnomAD-4.0.0	3.71754E-06	None	None	None	None	N	None	0	0	None	0	1.11478E-04	None	0	0	0	0	1.60031E-05
K/Q	rs376597164	0.208	0.998	N	0.727	0.341	None	gnomAD-2.1.1	7.14E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.56E-05	0
K/Q	rs376597164	0.208	0.998	N	0.727	0.341	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
K/Q	rs376597164	0.208	0.998	N	0.727	0.341	None	gnomAD-4.0.0	2.23069E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.05122E-05	0	0
K/T	rs752585224	0.017	0.999	N	0.68	0.353	0.370608029945	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	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	0.6872	likely_pathogenic	0.5713	pathogenic	0.018	Stabilizing	0.994	D	0.606	neutral	None	None	None	None	N
K/C	0.8999	likely_pathogenic	0.8483	pathogenic	-0.247	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
K/D	0.8136	likely_pathogenic	0.7477	pathogenic	0.218	Stabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	N
K/E	0.5008	ambiguous	0.4081	ambiguous	0.224	Stabilizing	0.992	D	0.598	neutral	N	0.518884234	None	None	N
K/F	0.9555	likely_pathogenic	0.9225	pathogenic	-0.206	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
K/G	0.6919	likely_pathogenic	0.5846	pathogenic	-0.172	Destabilizing	0.999	D	0.589	neutral	None	None	None	None	N
K/H	0.5451	ambiguous	0.4617	ambiguous	-0.424	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
K/I	0.8104	likely_pathogenic	0.7169	pathogenic	0.437	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
K/L	0.753	likely_pathogenic	0.6407	pathogenic	0.437	Stabilizing	0.998	D	0.589	neutral	None	None	None	None	N
K/M	0.6689	likely_pathogenic	0.5527	ambiguous	0.206	Stabilizing	1.0	D	0.741	deleterious	N	0.488462763	None	None	N
K/N	0.7234	likely_pathogenic	0.6213	pathogenic	0.241	Stabilizing	0.999	D	0.735	prob.delet.	N	0.503530779	None	None	N
K/P	0.7676	likely_pathogenic	0.6787	pathogenic	0.325	Stabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
K/Q	0.2977	likely_benign	0.2412	benign	0.077	Stabilizing	0.998	D	0.727	prob.delet.	N	0.520097742	None	None	N
K/R	0.093	likely_benign	0.0863	benign	-0.008	Destabilizing	0.467	N	0.28	neutral	N	0.491734918	None	None	N
K/S	0.7136	likely_pathogenic	0.6037	pathogenic	-0.273	Destabilizing	0.997	D	0.669	neutral	None	None	None	None	N
K/T	0.513	ambiguous	0.4021	ambiguous	-0.118	Destabilizing	0.999	D	0.68	prob.neutral	N	0.479232554	None	None	N
K/V	0.7364	likely_pathogenic	0.6279	pathogenic	0.325	Stabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	N
K/W	0.9178	likely_pathogenic	0.8818	pathogenic	-0.219	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
K/Y	0.8837	likely_pathogenic	0.8249	pathogenic	0.142	Stabilizing	1.0	D	0.743	deleterious	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.