TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4649	14170;14171;14172	chr2:178739288;178739287;178739286	chr2:179604015;179604014;179604013
N2AB	4332	13219;13220;13221	chr2:178739288;178739287;178739286	chr2:179604015;179604014;179604013
N2A	None	None	chr2:None	chr2:None
N2B	4286	13081;13082;13083	chr2:178739288;178739287;178739286	chr2:179604015;179604014;179604013
Novex-1	4411	13456;13457;13458	chr2:178739288;178739287;178739286	chr2:179604015;179604014;179604013
Novex-2	4478	13657;13658;13659	chr2:178739288;178739287;178739286	chr2:179604015;179604014;179604013
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: Ig-29
• Domain position: 44
• Structural Position: 115
• Q(SASA): 0.2501
• 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	rs1060500392	None	None	N	0.047	0.107	0.136095386433	gnomAD-4.0.0	6.84606E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.09924E-06	0	1.65772E-05
K/N	rs1574063706	None	0.001	N	0.072	0.147	0.117506650769	gnomAD-4.0.0	1.36939E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00019E-07	0	1.65815E-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	0.263	likely_benign	0.2609	benign	-0.658	Destabilizing	0.055	N	0.291	neutral	None	None	None	None	N
K/C	0.6084	likely_pathogenic	0.6156	pathogenic	-0.297	Destabilizing	0.958	D	0.461	neutral	None	None	None	None	N
K/D	0.3553	ambiguous	0.3562	ambiguous	-0.317	Destabilizing	0.055	N	0.312	neutral	None	None	None	None	N
K/E	0.1405	likely_benign	0.1465	benign	-0.195	Destabilizing	None	N	0.047	neutral	N	0.456798901	None	None	N
K/F	0.617	likely_pathogenic	0.6297	pathogenic	-0.295	Destabilizing	0.497	N	0.49	neutral	None	None	None	None	N
K/G	0.3608	ambiguous	0.3774	ambiguous	-1.024	Destabilizing	0.055	N	0.313	neutral	None	None	None	None	N
K/H	0.2636	likely_benign	0.2633	benign	-1.386	Destabilizing	0.497	N	0.4	neutral	None	None	None	None	N
K/I	0.2231	likely_benign	0.2244	benign	0.299	Stabilizing	0.124	N	0.531	neutral	None	None	None	None	N
K/L	0.2519	likely_benign	0.2568	benign	0.299	Stabilizing	0.02	N	0.319	neutral	None	None	None	None	N
K/M	0.1457	likely_benign	0.1457	benign	0.142	Stabilizing	0.007	N	0.185	neutral	N	0.479932667	None	None	N
K/N	0.2082	likely_benign	0.2092	benign	-0.358	Destabilizing	0.001	N	0.072	neutral	N	0.437881034	None	None	N
K/P	0.6143	likely_pathogenic	0.632	pathogenic	0.008	Stabilizing	0.364	N	0.455	neutral	None	None	None	None	N
K/Q	0.1345	likely_benign	0.1356	benign	-0.331	Destabilizing	0.096	N	0.268	neutral	D	0.531190107	None	None	N
K/R	0.0964	likely_benign	0.0992	benign	-0.656	Destabilizing	0.001	N	0.08	neutral	N	0.418772909	None	None	N
K/S	0.28	likely_benign	0.2824	benign	-0.877	Destabilizing	0.055	N	0.213	neutral	None	None	None	None	N
K/T	0.1216	likely_benign	0.1166	benign	-0.55	Destabilizing	0.081	N	0.349	neutral	N	0.446796766	None	None	N
K/V	0.2322	likely_benign	0.237	benign	0.008	Stabilizing	0.124	N	0.373	neutral	None	None	None	None	N
K/W	0.6822	likely_pathogenic	0.7014	pathogenic	-0.245	Destabilizing	0.958	D	0.488	neutral	None	None	None	None	N
K/Y	0.4204	ambiguous	0.4289	ambiguous	None	Stabilizing	0.667	D	0.46	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.