TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30319	91180;91181;91182	chr2:178551945;178551944;178551943	chr2:179416672;179416671;179416670
N2AB	28678	86257;86258;86259	chr2:178551945;178551944;178551943	chr2:179416672;179416671;179416670
N2A	27751	83476;83477;83478	chr2:178551945;178551944;178551943	chr2:179416672;179416671;179416670
N2B	21254	63985;63986;63987	chr2:178551945;178551944;178551943	chr2:179416672;179416671;179416670
Novex-1	21379	64360;64361;64362	chr2:178551945;178551944;178551943	chr2:179416672;179416671;179416670
Novex-2	21446	64561;64562;64563	chr2:178551945;178551944;178551943	chr2:179416672;179416671;179416670
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: Fn3-108
• Domain position: 96
• Structural Position: 131
• Q(SASA): 0.069
• 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	rs1171847318	-2.149	0.361	N	0.651	0.211	0.146414634003	gnomAD-4.0.0	1.59299E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86316E-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	0.3805	ambiguous	0.4964	ambiguous	-0.191	Destabilizing	0.236	N	0.571	neutral	None	None	None	None	N
K/C	0.6168	likely_pathogenic	0.6981	pathogenic	-0.09	Destabilizing	0.984	D	0.637	neutral	None	None	None	None	N
K/D	0.7003	likely_pathogenic	0.8072	pathogenic	-0.093	Destabilizing	0.272	N	0.586	neutral	None	None	None	None	N
K/E	0.1845	likely_benign	0.2643	benign	-0.026	Destabilizing	0.008	N	0.211	neutral	N	0.507019375	None	None	N
K/F	0.8469	likely_pathogenic	0.922	pathogenic	0.043	Stabilizing	0.942	D	0.669	prob.neutral	None	None	None	None	N
K/G	0.4987	ambiguous	0.6063	pathogenic	-0.515	Destabilizing	0.428	N	0.573	neutral	None	None	None	None	N
K/H	0.3309	likely_benign	0.3857	ambiguous	-0.935	Destabilizing	0.842	D	0.559	neutral	None	None	None	None	N
K/I	0.4972	ambiguous	0.6381	pathogenic	0.627	Stabilizing	0.8	D	0.72	deleterious	N	0.494425288	None	None	N
K/L	0.5047	ambiguous	0.6177	pathogenic	0.627	Stabilizing	0.428	N	0.575	neutral	None	None	None	None	N
K/M	0.3529	ambiguous	0.455	ambiguous	0.437	Stabilizing	0.942	D	0.531	neutral	None	None	None	None	N
K/N	0.5178	ambiguous	0.6412	pathogenic	-0.04	Destabilizing	0.361	N	0.651	prob.neutral	N	0.504767635	None	None	N
K/P	0.9356	likely_pathogenic	0.9636	pathogenic	0.384	Stabilizing	0.942	D	0.683	prob.neutral	None	None	None	None	N
K/Q	0.1134	likely_benign	0.1335	benign	-0.13	Destabilizing	0.022	N	0.207	neutral	N	0.500288191	None	None	N
K/R	0.0746	likely_benign	0.0777	benign	-0.488	Destabilizing	0.002	N	0.417	neutral	N	0.496133165	None	None	N
K/S	0.4184	ambiguous	0.544	ambiguous	-0.528	Destabilizing	0.428	N	0.555	neutral	None	None	None	None	N
K/T	0.2055	likely_benign	0.286	benign	-0.285	Destabilizing	0.361	N	0.614	neutral	D	0.522298259	None	None	N
K/V	0.3898	ambiguous	0.524	ambiguous	0.384	Stabilizing	0.603	D	0.609	neutral	None	None	None	None	N
K/W	0.8203	likely_pathogenic	0.8796	pathogenic	0.082	Stabilizing	0.984	D	0.645	neutral	None	None	None	None	N
K/Y	0.7324	likely_pathogenic	0.8247	pathogenic	0.357	Stabilizing	0.942	D	0.627	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.