TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26137	78634;78635;78636	chr2:178567723;178567722;178567721	chr2:179432450;179432449;179432448
N2AB	24496	73711;73712;73713	chr2:178567723;178567722;178567721	chr2:179432450;179432449;179432448
N2A	23569	70930;70931;70932	chr2:178567723;178567722;178567721	chr2:179432450;179432449;179432448
N2B	17072	51439;51440;51441	chr2:178567723;178567722;178567721	chr2:179432450;179432449;179432448
Novex-1	17197	51814;51815;51816	chr2:178567723;178567722;178567721	chr2:179432450;179432449;179432448
Novex-2	17264	52015;52016;52017	chr2:178567723;178567722;178567721	chr2:179432450;179432449;179432448
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: Fn3-78
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.2908
• 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	None	None	1.0	N	0.693	0.387	0.220303561663	gnomAD-4.0.0	6.84843E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00296E-07	0	0
K/R	None	None	0.999	N	0.539	0.309	0.321951552304	gnomAD-4.0.0	1.59477E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88452E-05	0	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	0.982	likely_pathogenic	0.9817	pathogenic	-0.537	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
K/C	0.9927	likely_pathogenic	0.9923	pathogenic	-0.595	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
K/D	0.9965	likely_pathogenic	0.9965	pathogenic	0.303	Stabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
K/E	0.9772	likely_pathogenic	0.9781	pathogenic	0.393	Stabilizing	0.999	D	0.59	neutral	N	0.506373509	None	None	N
K/F	0.9972	likely_pathogenic	0.997	pathogenic	-0.378	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
K/G	0.9892	likely_pathogenic	0.9895	pathogenic	-0.855	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
K/H	0.9313	likely_pathogenic	0.9272	pathogenic	-1.105	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
K/I	0.9765	likely_pathogenic	0.9721	pathogenic	0.264	Stabilizing	1.0	D	0.807	deleterious	N	0.476154951	None	None	N
K/L	0.9505	likely_pathogenic	0.9466	pathogenic	0.264	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
K/M	0.929	likely_pathogenic	0.9253	pathogenic	0.079	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
K/N	0.9904	likely_pathogenic	0.9904	pathogenic	-0.22	Destabilizing	1.0	D	0.693	prob.neutral	N	0.475292351	None	None	N
K/P	0.9757	likely_pathogenic	0.9763	pathogenic	0.027	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
K/Q	0.8492	likely_pathogenic	0.8538	pathogenic	-0.307	Destabilizing	1.0	D	0.666	neutral	N	0.513342341	None	None	N
K/R	0.1615	likely_benign	0.1601	benign	-0.353	Destabilizing	0.999	D	0.539	neutral	N	0.48775325	None	None	N
K/S	0.9926	likely_pathogenic	0.9926	pathogenic	-0.939	Destabilizing	0.999	D	0.622	neutral	None	None	None	None	N
K/T	0.9616	likely_pathogenic	0.9571	pathogenic	-0.647	Destabilizing	1.0	D	0.779	deleterious	N	0.505914936	None	None	N
K/V	0.9658	likely_pathogenic	0.9615	pathogenic	0.027	Stabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
K/W	0.9951	likely_pathogenic	0.9945	pathogenic	-0.235	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
K/Y	0.9883	likely_pathogenic	0.9876	pathogenic	0.06	Stabilizing	1.0	D	0.777	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.