TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24496	73711;73712;73713	chr2:178572646;178572645;178572644	chr2:179437373;179437372;179437371
N2AB	22855	68788;68789;68790	chr2:178572646;178572645;178572644	chr2:179437373;179437372;179437371
N2A	21928	66007;66008;66009	chr2:178572646;178572645;178572644	chr2:179437373;179437372;179437371
N2B	15431	46516;46517;46518	chr2:178572646;178572645;178572644	chr2:179437373;179437372;179437371
Novex-1	15556	46891;46892;46893	chr2:178572646;178572645;178572644	chr2:179437373;179437372;179437371
Novex-2	15623	47092;47093;47094	chr2:178572646;178572645;178572644	chr2:179437373;179437372;179437371
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-132
• Domain position: 66
• Structural Position: 153
• Q(SASA): 0.7064
• Predicted PPI site: I

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/T	rs1035751709	None	0.999	N	0.703	0.522	0.452928561435	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/T	rs1035751709	None	0.999	N	0.703	0.522	0.452928561435	gnomAD-4.0.0	6.57609E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47076E-05	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	0.9432	likely_pathogenic	0.9379	pathogenic	-1.021	Destabilizing	0.998	D	0.645	neutral	None	None	None	None	I
K/C	0.9413	likely_pathogenic	0.9447	pathogenic	-1.014	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
K/D	0.973	likely_pathogenic	0.9729	pathogenic	-0.768	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	I
K/E	0.859	likely_pathogenic	0.8401	pathogenic	-0.577	Destabilizing	0.996	D	0.649	neutral	N	0.486212989	None	None	I
K/F	0.9863	likely_pathogenic	0.9855	pathogenic	-0.42	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	I
K/G	0.96	likely_pathogenic	0.9579	pathogenic	-1.46	Destabilizing	1.0	D	0.612	neutral	None	None	None	None	I
K/H	0.665	likely_pathogenic	0.6785	pathogenic	-1.696	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
K/I	0.8769	likely_pathogenic	0.8784	pathogenic	0.171	Stabilizing	1.0	D	0.728	prob.delet.	D	0.536638567	None	None	I
K/L	0.869	likely_pathogenic	0.8684	pathogenic	0.171	Stabilizing	1.0	D	0.612	neutral	None	None	None	None	I
K/M	0.7973	likely_pathogenic	0.7975	pathogenic	0.017	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
K/N	0.9164	likely_pathogenic	0.9097	pathogenic	-1.088	Destabilizing	0.999	D	0.714	prob.delet.	N	0.496710375	None	None	I
K/P	0.9801	likely_pathogenic	0.9771	pathogenic	-0.199	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
K/Q	0.5149	ambiguous	0.4821	ambiguous	-1.012	Destabilizing	0.999	D	0.71	prob.delet.	N	0.49051863	None	None	I
K/R	0.0929	likely_benign	0.0974	benign	-0.925	Destabilizing	0.64	D	0.351	neutral	N	0.507374453	None	None	I
K/S	0.9406	likely_pathogenic	0.9343	pathogenic	-1.745	Destabilizing	0.998	D	0.687	prob.neutral	None	None	None	None	I
K/T	0.7881	likely_pathogenic	0.7749	pathogenic	-1.318	Destabilizing	0.999	D	0.703	prob.neutral	N	0.519322243	None	None	I
K/V	0.8646	likely_pathogenic	0.8643	pathogenic	-0.199	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
K/W	0.9692	likely_pathogenic	0.9696	pathogenic	-0.323	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
K/Y	0.9393	likely_pathogenic	0.9427	pathogenic	-0.024	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I

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.