TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6579	19960;19961;19962	chr2:178727843;178727842;178727841	chr2:179592570;179592569;179592568
N2AB	6262	19009;19010;19011	chr2:178727843;178727842;178727841	chr2:179592570;179592569;179592568
N2A	5335	16228;16229;16230	chr2:178727843;178727842;178727841	chr2:179592570;179592569;179592568
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-50
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.5679
• 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/N	rs1578112424	None	0.952	N	0.303	0.133	0.107399877778	gnomAD-4.0.0	3.27721E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.85566E-06	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	0.4376	ambiguous	0.4759	ambiguous	-0.42	Destabilizing	0.843	D	0.323	neutral	None	None	None	None	N
K/C	0.8349	likely_pathogenic	0.8468	pathogenic	-0.462	Destabilizing	0.999	D	0.355	neutral	None	None	None	None	N
K/D	0.7159	likely_pathogenic	0.7389	pathogenic	0.284	Stabilizing	0.867	D	0.321	neutral	None	None	None	None	N
K/E	0.2085	likely_benign	0.2253	benign	0.38	Stabilizing	0.038	N	0.119	neutral	N	0.492667919	None	None	N
K/F	0.8027	likely_pathogenic	0.8146	pathogenic	-0.211	Destabilizing	0.974	D	0.367	neutral	None	None	None	None	N
K/G	0.6358	likely_pathogenic	0.6981	pathogenic	-0.744	Destabilizing	0.963	D	0.361	neutral	None	None	None	None	N
K/H	0.4277	ambiguous	0.4582	ambiguous	-0.97	Destabilizing	0.992	D	0.313	neutral	None	None	None	None	N
K/I	0.3919	ambiguous	0.3861	ambiguous	0.399	Stabilizing	0.126	N	0.378	neutral	N	0.45466861	None	None	N
K/L	0.3884	ambiguous	0.4042	ambiguous	0.399	Stabilizing	0.161	N	0.35	neutral	None	None	None	None	N
K/M	0.2391	likely_benign	0.244	benign	0.112	Stabilizing	0.917	D	0.315	neutral	None	None	None	None	N
K/N	0.5285	ambiguous	0.5481	ambiguous	-0.144	Destabilizing	0.952	D	0.303	neutral	N	0.451119757	None	None	N
K/P	0.5318	ambiguous	0.579	pathogenic	0.156	Stabilizing	0.017	N	0.097	neutral	None	None	None	None	N
K/Q	0.1541	likely_benign	0.1652	benign	-0.188	Destabilizing	0.543	D	0.321	neutral	N	0.489398328	None	None	N
K/R	0.1116	likely_benign	0.116	benign	-0.311	Destabilizing	0.645	D	0.276	neutral	N	0.462385085	None	None	N
K/S	0.5307	ambiguous	0.5702	pathogenic	-0.8	Destabilizing	0.929	D	0.251	neutral	None	None	None	None	N
K/T	0.2446	likely_benign	0.2582	benign	-0.503	Destabilizing	0.746	D	0.319	neutral	N	0.461923725	None	None	N
K/V	0.397	ambiguous	0.4013	ambiguous	0.156	Stabilizing	0.007	N	0.254	neutral	None	None	None	None	N
K/W	0.8601	likely_pathogenic	0.876	pathogenic	-0.115	Destabilizing	0.999	D	0.457	neutral	None	None	None	None	N
K/Y	0.6939	likely_pathogenic	0.7149	pathogenic	0.183	Stabilizing	0.929	D	0.362	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.