TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26422	79489;79490;79491	chr2:178566868;178566867;178566866	chr2:179431595;179431594;179431593
N2AB	24781	74566;74567;74568	chr2:178566868;178566867;178566866	chr2:179431595;179431594;179431593
N2A	23854	71785;71786;71787	chr2:178566868;178566867;178566866	chr2:179431595;179431594;179431593
N2B	17357	52294;52295;52296	chr2:178566868;178566867;178566866	chr2:179431595;179431594;179431593
Novex-1	17482	52669;52670;52671	chr2:178566868;178566867;178566866	chr2:179431595;179431594;179431593
Novex-2	17549	52870;52871;52872	chr2:178566868;178566867;178566866	chr2:179431595;179431594;179431593
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-80
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.2441
• 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
I/L	rs1553590996	None	0.63	N	0.479	0.207	0.559156356702	gnomAD-4.0.0	2.73732E-06	None	None	None	None	N	None	0	0	None	0	1.00939E-04	None	0	0	0	0	0
I/T	rs3731745	-2.683	0.983	N	0.671	0.404	None	gnomAD-2.1.1	2.57346E-02	None	None	None	None	N	None	4.85155E-03	3.35052E-02	None	1.46289E-02	6.12056E-02	None	6.04733E-03	None	4.7937E-02	2.33536E-02	2.65748E-02
I/T	rs3731745	-2.683	0.983	N	0.671	0.404	None	gnomAD-3.1.2	2.023E-02	None	None	None	None	N	None	4.49189E-03	2.19131E-02	3.07018E-02	1.90311E-02	6.10465E-02	None	4.45974E-02	6.32911E-03	2.3392E-02	8.28844E-03	1.95985E-02
I/T	rs3731745	-2.683	0.983	N	0.671	0.404	None	1000 genomes	2.23642E-02	None	None	None	None	N	None	8E-04	2.45E-02	None	None	6.05E-02	2.68E-02	None	None	None	6.1E-03	None
I/T	rs3731745	-2.683	0.983	N	0.671	0.404	None	gnomAD-4.0.0	2.28872E-02	None	None	None	None	N	None	4.29448E-03	2.94029E-02	None	1.48689E-02	6.3117E-02	None	4.77173E-02	9.89772E-03	2.24368E-02	6.71981E-03	2.17106E-02
I/V	rs1553590996	None	0.598	N	0.487	0.143	0.513337797588	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	1.3113E-04	0	0	0	None	0	0	0	0	0
I/V	rs1553590996	None	0.598	N	0.487	0.143	0.513337797588	gnomAD-4.0.0	2.47925E-06	None	None	None	None	N	None	0	3.336E-05	None	0	0	None	0	0	1.69539E-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
I/A	0.4101	ambiguous	0.4148	ambiguous	-2.258	Highly Destabilizing	0.916	D	0.602	neutral	None	None	None	None	N
I/C	0.699	likely_pathogenic	0.7037	pathogenic	-1.503	Destabilizing	0.999	D	0.714	prob.delet.	None	None	None	None	N
I/D	0.9127	likely_pathogenic	0.9272	pathogenic	-1.999	Destabilizing	0.996	D	0.779	deleterious	None	None	None	None	N
I/E	0.8524	likely_pathogenic	0.8642	pathogenic	-1.901	Destabilizing	0.987	D	0.755	deleterious	None	None	None	None	N
I/F	0.1533	likely_benign	0.1627	benign	-1.432	Destabilizing	0.805	D	0.615	neutral	N	0.472583326	None	None	N
I/G	0.8204	likely_pathogenic	0.8399	pathogenic	-2.687	Highly Destabilizing	0.987	D	0.743	deleterious	None	None	None	None	N
I/H	0.5572	ambiguous	0.589	pathogenic	-1.858	Destabilizing	0.993	D	0.773	deleterious	None	None	None	None	N
I/K	0.7801	likely_pathogenic	0.7935	pathogenic	-1.668	Destabilizing	0.987	D	0.758	deleterious	None	None	None	None	N
I/L	0.1378	likely_benign	0.1565	benign	-1.089	Destabilizing	0.63	D	0.479	neutral	N	0.520537672	None	None	N
I/M	0.1173	likely_benign	0.1223	benign	-0.898	Destabilizing	0.994	D	0.679	prob.neutral	N	0.485852189	None	None	N
I/N	0.4713	ambiguous	0.5046	ambiguous	-1.667	Destabilizing	0.983	D	0.78	deleterious	N	0.47245474	None	None	N
I/P	0.9872	likely_pathogenic	0.9889	pathogenic	-1.453	Destabilizing	0.996	D	0.787	deleterious	None	None	None	None	N
I/Q	0.6847	likely_pathogenic	0.7004	pathogenic	-1.75	Destabilizing	0.987	D	0.787	deleterious	None	None	None	None	N
I/R	0.6491	likely_pathogenic	0.6531	pathogenic	-1.099	Destabilizing	0.987	D	0.785	deleterious	None	None	None	None	N
I/S	0.409	ambiguous	0.4277	ambiguous	-2.369	Highly Destabilizing	0.983	D	0.681	prob.neutral	N	0.479910252	None	None	N
I/T	0.2075	likely_benign	0.1993	benign	-2.148	Highly Destabilizing	0.983	D	0.671	neutral	N	0.511571472	None	None	N
I/V	0.0737	likely_benign	0.0733	benign	-1.453	Destabilizing	0.598	D	0.487	neutral	N	0.450043011	None	None	N
I/W	0.7228	likely_pathogenic	0.7479	pathogenic	-1.613	Destabilizing	0.997	D	0.767	deleterious	None	None	None	None	N
I/Y	0.5124	ambiguous	0.5321	ambiguous	-1.388	Destabilizing	0.033	N	0.501	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.