TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22795	68608;68609;68610	chr2:178578132;178578131;178578130	chr2:179442859;179442858;179442857
N2AB	21154	63685;63686;63687	chr2:178578132;178578131;178578130	chr2:179442859;179442858;179442857
N2A	20227	60904;60905;60906	chr2:178578132;178578131;178578130	chr2:179442859;179442858;179442857
N2B	13730	41413;41414;41415	chr2:178578132;178578131;178578130	chr2:179442859;179442858;179442857
Novex-1	13855	41788;41789;41790	chr2:178578132;178578131;178578130	chr2:179442859;179442858;179442857
Novex-2	13922	41989;41990;41991	chr2:178578132;178578131;178578130	chr2:179442859;179442858;179442857
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: Fn3-53
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.8677
• 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/R	rs1311571163	0.423	0.969	N	0.48	0.196	0.258779203287	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
K/R	rs1311571163	0.423	0.969	N	0.48	0.196	0.258779203287	gnomAD-4.0.0	1.59261E-06	None	None	None	None	I	None	0	2.28707E-05	None	0	0	None	0	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	0.5718	likely_pathogenic	0.4847	ambiguous	0.052	Stabilizing	0.91	D	0.497	neutral	None	None	None	None	I
K/C	0.8334	likely_pathogenic	0.7952	pathogenic	-0.34	Destabilizing	0.999	D	0.569	neutral	None	None	None	None	I
K/D	0.7332	likely_pathogenic	0.6983	pathogenic	-0.233	Destabilizing	0.986	D	0.431	neutral	None	None	None	None	I
K/E	0.4668	ambiguous	0.4062	ambiguous	-0.25	Destabilizing	0.939	D	0.502	neutral	N	0.503202705	None	None	I
K/F	0.931	likely_pathogenic	0.8975	pathogenic	-0.298	Destabilizing	0.993	D	0.551	neutral	None	None	None	None	I
K/G	0.6279	likely_pathogenic	0.5607	ambiguous	-0.073	Destabilizing	0.953	D	0.389	neutral	None	None	None	None	I
K/H	0.46	ambiguous	0.4183	ambiguous	-0.198	Destabilizing	0.999	D	0.46	neutral	None	None	None	None	I
K/I	0.6779	likely_pathogenic	0.6019	pathogenic	0.297	Stabilizing	0.986	D	0.539	neutral	None	None	None	None	I
K/L	0.6315	likely_pathogenic	0.5747	pathogenic	0.297	Stabilizing	0.91	D	0.405	neutral	None	None	None	None	I
K/M	0.5384	ambiguous	0.4741	ambiguous	-0.018	Destabilizing	0.999	D	0.455	neutral	N	0.491688312	None	None	I
K/N	0.6525	likely_pathogenic	0.6117	pathogenic	0.126	Stabilizing	0.982	D	0.473	neutral	N	0.467454764	None	None	I
K/P	0.6555	likely_pathogenic	0.6045	pathogenic	0.239	Stabilizing	0.993	D	0.467	neutral	None	None	None	None	I
K/Q	0.2537	likely_benign	0.2161	benign	-0.029	Destabilizing	0.991	D	0.519	neutral	N	0.474318072	None	None	I
K/R	0.09	likely_benign	0.0837	benign	-0.046	Destabilizing	0.969	D	0.48	neutral	N	0.517036007	None	None	I
K/S	0.6266	likely_pathogenic	0.5684	pathogenic	-0.244	Destabilizing	0.91	D	0.488	neutral	None	None	None	None	I
K/T	0.3551	ambiguous	0.3151	benign	-0.146	Destabilizing	0.17	N	0.359	neutral	N	0.498450246	None	None	I
K/V	0.5903	likely_pathogenic	0.5106	ambiguous	0.239	Stabilizing	0.91	D	0.378	neutral	None	None	None	None	I
K/W	0.9035	likely_pathogenic	0.8594	pathogenic	-0.402	Destabilizing	0.999	D	0.627	neutral	None	None	None	None	I
K/Y	0.8282	likely_pathogenic	0.7766	pathogenic	-0.044	Destabilizing	0.998	D	0.481	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.