TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17618	53077;53078;53079	chr2:178607935;178607934;178607933	chr2:179472662;179472661;179472660
N2AB	15977	48154;48155;48156	chr2:178607935;178607934;178607933	chr2:179472662;179472661;179472660
N2A	15050	45373;45374;45375	chr2:178607935;178607934;178607933	chr2:179472662;179472661;179472660
N2B	8553	25882;25883;25884	chr2:178607935;178607934;178607933	chr2:179472662;179472661;179472660
Novex-1	8678	26257;26258;26259	chr2:178607935;178607934;178607933	chr2:179472662;179472661;179472660
Novex-2	8745	26458;26459;26460	chr2:178607935;178607934;178607933	chr2:179472662;179472661;179472660
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: Fn3-16
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.4502
• 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	rs201213901	-0.506	1.0	N	0.743	0.494	None	gnomAD-2.1.1	1.00373E-03	None	None	None	None	N	None	4.13565E-04	5.66E-05	None	9.67E-05	0	None	0	None	4.39683E-04	1.95361E-03	9.82594E-04
R/C	rs201213901	-0.506	1.0	N	0.743	0.494	None	gnomAD-3.1.2	8.29723E-04	None	None	None	None	N	None	3.14025E-04	6.57E-05	0	5.77034E-04	0	None	4.71965E-04	0	1.54639E-03	0	0
R/C	rs201213901	-0.506	1.0	N	0.743	0.494	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	1E-03	None	None	None	0	None
R/C	rs201213901	-0.506	1.0	N	0.743	0.494	None	gnomAD-4.0.0	1.32556E-03	None	None	None	None	N	None	2.93545E-04	3.33589E-05	None	2.02867E-04	0	None	4.84466E-04	0	1.72141E-03	0	7.52795E-04
R/H	rs371538664	-1.41	1.0	N	0.794	0.46	None	gnomAD-2.1.1	1.8931E-04	None	None	None	None	N	None	4.14E-05	2.83E-05	None	3.57695E-03	1.54767E-04	None	0	None	0	7.03E-05	2.8082E-04
R/H	rs371538664	-1.41	1.0	N	0.794	0.46	None	gnomAD-3.1.2	1.5803E-04	None	None	None	None	N	None	0	0	0	5.48182E-03	1.95084E-04	None	0	0	5.89E-05	0	0
R/H	rs371538664	-1.41	1.0	N	0.794	0.46	None	gnomAD-4.0.0	1.34549E-04	None	None	None	None	N	None	1.33629E-05	3.33712E-05	None	4.22611E-03	2.01234E-04	None	0	4.93746E-04	5.25751E-05	0	2.40323E-04
R/S	rs201213901	-0.647	1.0	N	0.744	0.384	0.386234084001	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
R/S	rs201213901	-0.647	1.0	N	0.744	0.384	0.386234084001	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/S	rs201213901	-0.647	1.0	N	0.744	0.384	0.386234084001	gnomAD-4.0.0	1.05408E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.18717E-05	0	4.80677E-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
R/A	0.8448	likely_pathogenic	0.7875	pathogenic	-1.057	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
R/C	0.3775	ambiguous	0.2936	benign	-0.963	Destabilizing	1.0	D	0.743	deleterious	N	0.489917567	None	None	N
R/D	0.972	likely_pathogenic	0.953	pathogenic	-0.186	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
R/E	0.8171	likely_pathogenic	0.7448	pathogenic	-0.079	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
R/F	0.9145	likely_pathogenic	0.8687	pathogenic	-1.051	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
R/G	0.8169	likely_pathogenic	0.7246	pathogenic	-1.339	Destabilizing	1.0	D	0.672	neutral	N	0.474179942	None	None	N
R/H	0.2178	likely_benign	0.1735	benign	-1.666	Destabilizing	1.0	D	0.794	deleterious	N	0.475265897	None	None	N
R/I	0.6972	likely_pathogenic	0.6143	pathogenic	-0.302	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
R/K	0.2096	likely_benign	0.1882	benign	-1.031	Destabilizing	0.998	D	0.558	neutral	None	None	None	None	N
R/L	0.6161	likely_pathogenic	0.5392	ambiguous	-0.302	Destabilizing	1.0	D	0.672	neutral	N	0.503589494	None	None	N
R/M	0.7783	likely_pathogenic	0.6987	pathogenic	-0.482	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
R/N	0.9322	likely_pathogenic	0.9012	pathogenic	-0.416	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
R/P	0.79	likely_pathogenic	0.714	pathogenic	-0.534	Destabilizing	1.0	D	0.741	deleterious	N	0.478019046	None	None	N
R/Q	0.2322	likely_benign	0.1877	benign	-0.665	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
R/S	0.9016	likely_pathogenic	0.8589	pathogenic	-1.252	Destabilizing	1.0	D	0.744	deleterious	N	0.501682552	None	None	N
R/T	0.7315	likely_pathogenic	0.6628	pathogenic	-0.971	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
R/V	0.764	likely_pathogenic	0.6868	pathogenic	-0.534	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
R/W	0.5675	likely_pathogenic	0.459	ambiguous	-0.689	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
R/Y	0.8143	likely_pathogenic	0.7279	pathogenic	-0.396	Destabilizing	1.0	D	0.749	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.