TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26440	79543;79544;79545	chr2:178566814;178566813;178566812	chr2:179431541;179431540;179431539
N2AB	24799	74620;74621;74622	chr2:178566814;178566813;178566812	chr2:179431541;179431540;179431539
N2A	23872	71839;71840;71841	chr2:178566814;178566813;178566812	chr2:179431541;179431540;179431539
N2B	17375	52348;52349;52350	chr2:178566814;178566813;178566812	chr2:179431541;179431540;179431539
Novex-1	17500	52723;52724;52725	chr2:178566814;178566813;178566812	chr2:179431541;179431540;179431539
Novex-2	17567	52924;52925;52926	chr2:178566814;178566813;178566812	chr2:179431541;179431540;179431539
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Fn3-80
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.4287
• 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
R/C	rs55861600	-0.487	0.997	D	0.683	0.331	None	gnomAD-2.1.1	2.51621E-03	None	None	None	None	N	None	2.60348E-02	1.38795E-03	None	0	0	None	2.61489E-04	None	0	8.61E-05	8.43645E-04
R/C	rs55861600	-0.487	0.997	D	0.683	0.331	None	gnomAD-3.1.2	7.51355E-03	None	None	None	None	N	None	2.59991E-02	2.62398E-03	0	0	0	None	0	3.16456E-03	1.47098E-04	4.14938E-04	6.20821E-03
R/C	rs55861600	-0.487	0.997	D	0.683	0.331	None	1000 genomes	6.58946E-03	None	None	None	None	N	None	2.19E-02	4.3E-03	None	None	1E-03	0	None	None	None	0	None
R/C	rs55861600	-0.487	0.997	D	0.683	0.331	None	gnomAD-4.0.0	1.471E-03	None	None	None	None	N	None	2.69217E-02	1.7844E-03	None	0	4.46708E-05	None	0	1.1555E-03	7.54471E-05	2.08635E-04	2.09728E-03
R/H	rs56044609	-1.351	0.096	N	0.243	0.102	None	gnomAD-2.1.1	1.76438E-03	None	None	None	None	N	None	1.59315E-02	1.58595E-03	None	0	0	None	5.22944E-04	None	8.08E-05	1.80087E-04	1.54625E-03
R/H	rs56044609	-1.351	0.096	N	0.243	0.102	None	gnomAD-3.1.2	5.02513E-03	None	None	None	None	N	None	1.66127E-02	2.69064E-03	0	0	0	None	0	9.49367E-03	2.20614E-04	1.03648E-03	5.73066E-03
R/H	rs56044609	-1.351	0.096	N	0.243	0.102	None	1000 genomes	4.59265E-03	None	None	None	None	N	None	1.74E-02	0	None	None	0	0	None	None	None	0	None
R/H	rs56044609	-1.351	0.096	N	0.243	0.102	None	gnomAD-4.0.0	1.05004E-03	None	None	None	None	N	None	1.68031E-02	2.08479E-03	None	0	4.46488E-05	None	4.70544E-05	2.64026E-03	9.32463E-05	6.47825E-04	1.9051E-03
R/L	rs56044609	None	0.768	N	0.59	0.33	0.415313616471	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	9.42E-05	0	0	0	0
R/L	rs56044609	None	0.768	N	0.59	0.33	0.415313616471	gnomAD-4.0.0	6.5773E-06	None	None	None	None	N	None	0	0	None	0	0	None	9.42152E-05	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
R/A	0.3502	ambiguous	0.3432	ambiguous	-0.077	Destabilizing	0.011	N	0.266	neutral	None	None	None	None	N
R/C	0.1737	likely_benign	0.1833	benign	-0.277	Destabilizing	0.997	D	0.683	prob.neutral	D	0.52271676	None	None	N
R/D	0.7119	likely_pathogenic	0.7256	pathogenic	-0.052	Destabilizing	0.923	D	0.579	neutral	None	None	None	None	N
R/E	0.4489	ambiguous	0.439	ambiguous	0.015	Stabilizing	0.775	D	0.466	neutral	None	None	None	None	N
R/F	0.5534	ambiguous	0.5569	ambiguous	-0.271	Destabilizing	0.923	D	0.677	prob.neutral	None	None	None	None	N
R/G	0.2629	likely_benign	0.2615	benign	-0.276	Destabilizing	0.768	D	0.551	neutral	N	0.483059506	None	None	N
R/H	0.1201	likely_benign	0.1184	benign	-0.688	Destabilizing	0.096	N	0.243	neutral	N	0.503688282	None	None	N
R/I	0.2701	likely_benign	0.2896	benign	0.412	Stabilizing	0.923	D	0.677	prob.neutral	None	None	None	None	N
R/K	0.109	likely_benign	0.1083	benign	-0.157	Destabilizing	0.587	D	0.465	neutral	None	None	None	None	N
R/L	0.2142	likely_benign	0.2271	benign	0.412	Stabilizing	0.768	D	0.59	neutral	N	0.435673778	None	None	N
R/M	0.2754	likely_benign	0.2855	benign	-0.026	Destabilizing	0.996	D	0.627	neutral	None	None	None	None	N
R/N	0.5179	ambiguous	0.5234	ambiguous	0.072	Stabilizing	0.633	D	0.507	neutral	None	None	None	None	N
R/P	0.2617	likely_benign	0.2883	benign	0.269	Stabilizing	0.979	D	0.664	neutral	N	0.38676511	None	None	N
R/Q	0.1077	likely_benign	0.0965	benign	-0.036	Destabilizing	0.923	D	0.552	neutral	None	None	None	None	N
R/S	0.4452	ambiguous	0.4399	ambiguous	-0.324	Destabilizing	0.768	D	0.534	neutral	N	0.467572766	None	None	N
R/T	0.2122	likely_benign	0.2211	benign	-0.121	Destabilizing	0.775	D	0.579	neutral	None	None	None	None	N
R/V	0.3143	likely_benign	0.3241	benign	0.269	Stabilizing	0.858	D	0.559	neutral	None	None	None	None	N
R/W	0.2188	likely_benign	0.2106	benign	-0.288	Destabilizing	0.996	D	0.735	prob.delet.	None	None	None	None	N
R/Y	0.41	ambiguous	0.403	ambiguous	0.11	Stabilizing	0.858	D	0.681	prob.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.