TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29141	87646;87647;87648	chr2:178557933;178557932;178557931	chr2:179422660;179422659;179422658
N2AB	27500	82723;82724;82725	chr2:178557933;178557932;178557931	chr2:179422660;179422659;179422658
N2A	26573	79942;79943;79944	chr2:178557933;178557932;178557931	chr2:179422660;179422659;179422658
N2B	20076	60451;60452;60453	chr2:178557933;178557932;178557931	chr2:179422660;179422659;179422658
Novex-1	20201	60826;60827;60828	chr2:178557933;178557932;178557931	chr2:179422660;179422659;179422658
Novex-2	20268	61027;61028;61029	chr2:178557933;178557932;178557931	chr2:179422660;179422659;179422658
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-100
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.0952
• 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
P/A	None	None	0.039	D	0.613	0.654	0.449088463789	gnomAD-4.0.0	1.59295E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-05	0
P/S	None	None	0.865	D	0.796	0.739	0.603797353847	gnomAD-4.0.0	3.18589E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71562E-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
P/A	0.4922	ambiguous	0.651	pathogenic	-2.251	Highly Destabilizing	0.039	N	0.613	neutral	D	0.59674486	None	None	N
P/C	0.8792	likely_pathogenic	0.8925	pathogenic	-2.009	Highly Destabilizing	0.998	D	0.918	deleterious	None	None	None	None	N
P/D	0.999	likely_pathogenic	0.9995	pathogenic	-3.407	Highly Destabilizing	0.992	D	0.827	deleterious	None	None	None	None	N
P/E	0.9959	likely_pathogenic	0.9975	pathogenic	-3.155	Highly Destabilizing	0.983	D	0.811	deleterious	None	None	None	None	N
P/F	0.9975	likely_pathogenic	0.9987	pathogenic	-1.184	Destabilizing	0.998	D	0.923	deleterious	None	None	None	None	N
P/G	0.9798	likely_pathogenic	0.9901	pathogenic	-2.793	Highly Destabilizing	0.895	D	0.845	deleterious	None	None	None	None	N
P/H	0.9961	likely_pathogenic	0.9977	pathogenic	-2.654	Highly Destabilizing	0.999	D	0.899	deleterious	None	None	None	None	N
P/I	0.7873	likely_pathogenic	0.8108	pathogenic	-0.705	Destabilizing	0.983	D	0.903	deleterious	None	None	None	None	N
P/K	0.9976	likely_pathogenic	0.9985	pathogenic	-1.958	Destabilizing	0.983	D	0.809	deleterious	None	None	None	None	N
P/L	0.8147	likely_pathogenic	0.8701	pathogenic	-0.705	Destabilizing	0.957	D	0.865	deleterious	D	0.654755663	None	None	N
P/M	0.9615	likely_pathogenic	0.975	pathogenic	-1.013	Destabilizing	0.999	D	0.903	deleterious	None	None	None	None	N
P/N	0.9975	likely_pathogenic	0.9985	pathogenic	-2.454	Highly Destabilizing	0.992	D	0.882	deleterious	None	None	None	None	N
P/Q	0.991	likely_pathogenic	0.9946	pathogenic	-2.213	Highly Destabilizing	0.989	D	0.826	deleterious	D	0.654755663	None	None	N
P/R	0.9929	likely_pathogenic	0.9954	pathogenic	-1.85	Destabilizing	0.978	D	0.883	deleterious	D	0.654957467	None	None	N
P/S	0.942	likely_pathogenic	0.9694	pathogenic	-2.956	Highly Destabilizing	0.865	D	0.796	deleterious	D	0.654755663	None	None	N
P/T	0.8748	likely_pathogenic	0.9123	pathogenic	-2.571	Highly Destabilizing	0.978	D	0.809	deleterious	D	0.638705942	None	None	N
P/V	0.5228	ambiguous	0.5355	ambiguous	-1.199	Destabilizing	0.968	D	0.853	deleterious	None	None	None	None	N
P/W	0.9997	likely_pathogenic	0.9998	pathogenic	-1.84	Destabilizing	0.999	D	0.868	deleterious	None	None	None	None	N
P/Y	0.999	likely_pathogenic	0.9995	pathogenic	-1.501	Destabilizing	0.999	D	0.924	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.