TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33113	99562;99563;99564	chr2:178537870;178537869;178537868	chr2:179402597;179402596;179402595
N2AB	31472	94639;94640;94641	chr2:178537870;178537869;178537868	chr2:179402597;179402596;179402595
N2A	30545	91858;91859;91860	chr2:178537870;178537869;178537868	chr2:179402597;179402596;179402595
N2B	24048	72367;72368;72369	chr2:178537870;178537869;178537868	chr2:179402597;179402596;179402595
Novex-1	24173	72742;72743;72744	chr2:178537870;178537869;178537868	chr2:179402597;179402596;179402595
Novex-2	24240	72943;72944;72945	chr2:178537870;178537869;178537868	chr2:179402597;179402596;179402595
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-156
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.5119
• 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/E	None	None	0.29	N	0.551	0.209	0.260735089382	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.5324	ambiguous	0.4612	ambiguous	-0.145	Destabilizing	0.643	D	0.574	neutral	None	None	None	None	N
K/C	0.8619	likely_pathogenic	0.8376	pathogenic	-0.315	Destabilizing	0.997	D	0.715	prob.delet.	None	None	None	None	N
K/D	0.861	likely_pathogenic	0.7921	pathogenic	-0.045	Destabilizing	0.643	D	0.562	neutral	None	None	None	None	N
K/E	0.378	ambiguous	0.2948	benign	-0.032	Destabilizing	0.29	N	0.551	neutral	N	0.445555203	None	None	N
K/F	0.905	likely_pathogenic	0.8625	pathogenic	-0.272	Destabilizing	0.969	D	0.673	neutral	None	None	None	None	N
K/G	0.7529	likely_pathogenic	0.6765	pathogenic	-0.375	Destabilizing	0.643	D	0.615	neutral	None	None	None	None	N
K/H	0.5197	ambiguous	0.4709	ambiguous	-0.669	Destabilizing	0.839	D	0.547	neutral	None	None	None	None	N
K/I	0.4775	ambiguous	0.4239	ambiguous	0.388	Stabilizing	0.362	N	0.673	neutral	N	0.499293687	None	None	N
K/L	0.4929	ambiguous	0.4418	ambiguous	0.388	Stabilizing	0.27	N	0.57	neutral	None	None	None	None	N
K/M	0.3746	ambiguous	0.3205	benign	0.276	Stabilizing	0.92	D	0.547	neutral	None	None	None	None	N
K/N	0.685	likely_pathogenic	0.5898	pathogenic	0.041	Stabilizing	0.019	N	0.339	neutral	N	0.497792177	None	None	N
K/P	0.7511	likely_pathogenic	0.7284	pathogenic	0.24	Stabilizing	0.962	D	0.557	neutral	None	None	None	None	N
K/Q	0.2118	likely_benign	0.1856	benign	-0.181	Destabilizing	0.002	N	0.325	neutral	N	0.472683089	None	None	N
K/R	0.1005	likely_benign	0.0956	benign	-0.163	Destabilizing	0.201	N	0.521	neutral	N	0.458753787	None	None	N
K/S	0.6714	likely_pathogenic	0.5814	pathogenic	-0.497	Destabilizing	0.643	D	0.543	neutral	None	None	None	None	N
K/T	0.3064	likely_benign	0.2538	benign	-0.329	Destabilizing	0.449	N	0.542	neutral	N	0.486036388	None	None	N
K/V	0.4153	ambiguous	0.371	ambiguous	0.24	Stabilizing	0.328	N	0.601	neutral	None	None	None	None	N
K/W	0.9312	likely_pathogenic	0.9041	pathogenic	-0.214	Destabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	N
K/Y	0.8291	likely_pathogenic	0.781	pathogenic	0.116	Stabilizing	0.544	D	0.645	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.