TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32763	98512;98513;98514	chr2:178539778;178539777;178539776	chr2:179404505;179404504;179404503
N2AB	31122	93589;93590;93591	chr2:178539778;178539777;178539776	chr2:179404505;179404504;179404503
N2A	30195	90808;90809;90810	chr2:178539778;178539777;178539776	chr2:179404505;179404504;179404503
N2B	23698	71317;71318;71319	chr2:178539778;178539777;178539776	chr2:179404505;179404504;179404503
Novex-1	23823	71692;71693;71694	chr2:178539778;178539777;178539776	chr2:179404505;179404504;179404503
Novex-2	23890	71893;71894;71895	chr2:178539778;178539777;178539776	chr2:179404505;179404504;179404503
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-155
• Domain position: 56
• Structural Position: 141
• Q(SASA): 0.633
• 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/R	rs879242471	0.045	0.1	N	0.421	0.139	None	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	1.29199E-04	0	None	0	0	None	0	None	0	0	0
K/R	rs879242471	0.045	0.1	N	0.421	0.139	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
K/R	rs879242471	0.045	0.1	N	0.421	0.139	None	gnomAD-4.0.0	4.33772E-06	None	None	None	None	N	None	9.34205E-05	0	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	0.8058	likely_pathogenic	0.8116	pathogenic	0.023	Stabilizing	0.953	D	0.557	neutral	None	None	None	None	N
K/C	0.921	likely_pathogenic	0.923	pathogenic	-0.365	Destabilizing	0.999	D	0.658	neutral	None	None	None	None	N
K/D	0.9292	likely_pathogenic	0.9365	pathogenic	-0.129	Destabilizing	0.993	D	0.524	neutral	None	None	None	None	N
K/E	0.5829	likely_pathogenic	0.5939	pathogenic	-0.098	Destabilizing	0.939	D	0.559	neutral	N	0.488036544	None	None	N
K/F	0.9686	likely_pathogenic	0.966	pathogenic	-0.092	Destabilizing	0.998	D	0.649	neutral	None	None	None	None	N
K/G	0.8428	likely_pathogenic	0.8494	pathogenic	-0.192	Destabilizing	0.976	D	0.525	neutral	None	None	None	None	N
K/H	0.674	likely_pathogenic	0.6686	pathogenic	-0.333	Destabilizing	0.998	D	0.56	neutral	None	None	None	None	N
K/I	0.8395	likely_pathogenic	0.8416	pathogenic	0.52	Stabilizing	0.982	D	0.659	neutral	D	0.534118337	None	None	N
K/L	0.7403	likely_pathogenic	0.7427	pathogenic	0.52	Stabilizing	0.953	D	0.533	neutral	None	None	None	None	N
K/M	0.6586	likely_pathogenic	0.6601	pathogenic	0.063	Stabilizing	0.999	D	0.564	neutral	None	None	None	None	N
K/N	0.8765	likely_pathogenic	0.8834	pathogenic	None	Stabilizing	0.982	D	0.5	neutral	N	0.508566531	None	None	N
K/P	0.8602	likely_pathogenic	0.8632	pathogenic	0.382	Stabilizing	0.998	D	0.566	neutral	None	None	None	None	N
K/Q	0.3603	ambiguous	0.3632	ambiguous	-0.096	Destabilizing	0.982	D	0.537	neutral	N	0.517954019	None	None	N
K/R	0.1084	likely_benign	0.1095	benign	-0.098	Destabilizing	0.1	N	0.421	neutral	N	0.432625978	None	None	N
K/S	0.8541	likely_pathogenic	0.8597	pathogenic	-0.409	Destabilizing	0.91	D	0.552	neutral	None	None	None	None	N
K/T	0.5955	likely_pathogenic	0.6131	pathogenic	-0.227	Destabilizing	0.322	N	0.424	neutral	N	0.503275355	None	None	N
K/V	0.7933	likely_pathogenic	0.8038	pathogenic	0.382	Stabilizing	0.986	D	0.5	neutral	None	None	None	None	N
K/W	0.9329	likely_pathogenic	0.9289	pathogenic	-0.153	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
K/Y	0.9151	likely_pathogenic	0.9116	pathogenic	0.188	Stabilizing	0.998	D	0.629	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.