TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17043	51352;51353;51354	chr2:178611002;178611001;178611000	chr2:179475729;179475728;179475727
N2AB	15402	46429;46430;46431	chr2:178611002;178611001;178611000	chr2:179475729;179475728;179475727
N2A	14475	43648;43649;43650	chr2:178611002;178611001;178611000	chr2:179475729;179475728;179475727
N2B	7978	24157;24158;24159	chr2:178611002;178611001;178611000	chr2:179475729;179475728;179475727
Novex-1	8103	24532;24533;24534	chr2:178611002;178611001;178611000	chr2:179475729;179475728;179475727
Novex-2	8170	24733;24734;24735	chr2:178611002;178611001;178611000	chr2:179475729;179475728;179475727
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-111
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.6903
• 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/Q	rs794729269	None	0.975	N	0.694	0.358	None	gnomAD-4.0.0	4.10937E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.40056E-06	0	0
K/R	rs758910983	-0.006	0.787	N	0.589	0.273	0.407357902709	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.61E-05	None	0	0	0
K/R	rs758910983	-0.006	0.787	N	0.589	0.273	0.407357902709	gnomAD-4.0.0	2.73967E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80024E-06	2.32683E-05	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	0.6134	likely_pathogenic	0.5813	pathogenic	-0.584	Destabilizing	0.547	D	0.606	neutral	None	None	None	None	N
K/C	0.8568	likely_pathogenic	0.8341	pathogenic	-0.615	Destabilizing	0.985	D	0.755	deleterious	None	None	None	None	N
K/D	0.792	likely_pathogenic	0.7794	pathogenic	-0.135	Destabilizing	0.945	D	0.724	prob.delet.	None	None	None	None	N
K/E	0.3399	likely_benign	0.3386	benign	-0.005	Destabilizing	0.787	D	0.588	neutral	N	0.510708286	None	None	N
K/F	0.9164	likely_pathogenic	0.9133	pathogenic	-0.141	Destabilizing	0.894	D	0.757	deleterious	None	None	None	None	N
K/G	0.8235	likely_pathogenic	0.8036	pathogenic	-0.976	Destabilizing	0.945	D	0.645	neutral	None	None	None	None	N
K/H	0.3839	ambiguous	0.3622	ambiguous	-1.264	Destabilizing	0.995	D	0.673	neutral	None	None	None	None	N
K/I	0.5186	ambiguous	0.5091	ambiguous	0.441	Stabilizing	0.523	D	0.673	neutral	N	0.514093262	None	None	N
K/L	0.5785	likely_pathogenic	0.5554	ambiguous	0.441	Stabilizing	0.547	D	0.622	neutral	None	None	None	None	N
K/M	0.3662	ambiguous	0.3424	ambiguous	0.237	Stabilizing	0.97	D	0.677	prob.neutral	None	None	None	None	N
K/N	0.5497	ambiguous	0.5466	ambiguous	-0.57	Destabilizing	0.975	D	0.683	prob.neutral	N	0.50658342	None	None	N
K/P	0.9837	likely_pathogenic	0.9785	pathogenic	0.13	Stabilizing	0.981	D	0.731	prob.delet.	None	None	None	None	N
K/Q	0.1994	likely_benign	0.1928	benign	-0.577	Destabilizing	0.975	D	0.694	prob.neutral	N	0.510231113	None	None	N
K/R	0.1117	likely_benign	0.1082	benign	-0.717	Destabilizing	0.787	D	0.589	neutral	N	0.501031843	None	None	N
K/S	0.6142	likely_pathogenic	0.601	pathogenic	-1.222	Destabilizing	0.707	D	0.633	neutral	None	None	None	None	N
K/T	0.2309	likely_benign	0.2181	benign	-0.876	Destabilizing	0.864	D	0.688	prob.neutral	N	0.470095542	None	None	N
K/V	0.4958	ambiguous	0.4707	ambiguous	0.13	Stabilizing	0.017	N	0.484	neutral	None	None	None	None	N
K/W	0.9113	likely_pathogenic	0.9013	pathogenic	-0.028	Destabilizing	0.995	D	0.761	deleterious	None	None	None	None	N
K/Y	0.8355	likely_pathogenic	0.8255	pathogenic	0.244	Stabilizing	0.945	D	0.738	prob.delet.	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.