TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15627	47104;47105;47106	chr2:178618671;178618670;178618669	chr2:179483398;179483397;179483396
N2AB	13986	42181;42182;42183	chr2:178618671;178618670;178618669	chr2:179483398;179483397;179483396
N2A	13059	39400;39401;39402	chr2:178618671;178618670;178618669	chr2:179483398;179483397;179483396
N2B	6562	19909;19910;19911	chr2:178618671;178618670;178618669	chr2:179483398;179483397;179483396
Novex-1	6687	20284;20285;20286	chr2:178618671;178618670;178618669	chr2:179483398;179483397;179483396
Novex-2	6754	20485;20486;20487	chr2:178618671;178618670;178618669	chr2:179483398;179483397;179483396
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-108
• Domain position: 60
• Structural Position: 144
• Q(SASA): 0.1148
• 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
A/D	rs115813214	-2.53	0.968	N	0.663	0.61	0.72038618509	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
A/D	rs115813214	-2.53	0.968	N	0.663	0.61	0.72038618509	gnomAD-4.0.0	6.84837E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65893E-05
A/P	None	None	0.011	N	0.399	0.276	0.260735089382	gnomAD-4.0.0	6.84825E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00019E-07	0	0
A/S	None	None	0.811	N	0.541	0.224	0.265010934533	gnomAD-4.0.0	6.84825E-07	None	None	None	None	N	None	0	0	None	0	2.52781E-05	None	0	0	0	0	0
A/T	rs1576520581	None	0.103	N	0.385	0.245	0.225215365344	gnomAD-4.0.0	6.84825E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65893E-05
A/V	rs115813214	-0.588	0.811	N	0.571	0.258	None	gnomAD-2.1.1	5.66105E-04	None	None	None	None	N	None	5.92132E-03	3.97886E-04	None	0	0	None	0	None	0	7.84E-06	0
A/V	rs115813214	-0.588	0.811	N	0.571	0.258	None	gnomAD-3.1.2	1.44356E-03	None	None	None	None	N	None	5.01089E-03	5.91483E-04	0	0	0	None	0	0	0	0	1.44231E-03
A/V	rs115813214	-0.588	0.811	N	0.571	0.258	None	1000 genomes	7.98722E-04	None	None	None	None	N	None	3E-03	0	None	None	0	0	None	None	None	0	None
A/V	rs115813214	-0.588	0.811	N	0.571	0.258	None	gnomAD-4.0.0	2.65504E-04	None	None	None	None	N	None	5.08021E-03	4.34434E-04	None	0	0	None	0	8.27267E-04	1.69644E-06	1.09917E-05	2.24424E-04

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
A/C	0.5414	ambiguous	0.5576	ambiguous	-1.324	Destabilizing	0.999	D	0.618	neutral	None	None	None	None	N
A/D	0.9493	likely_pathogenic	0.9646	pathogenic	-2.306	Highly Destabilizing	0.968	D	0.663	neutral	N	0.52166936	None	None	N
A/E	0.9244	likely_pathogenic	0.9392	pathogenic	-2.258	Highly Destabilizing	0.919	D	0.636	neutral	None	None	None	None	N
A/F	0.9028	likely_pathogenic	0.926	pathogenic	-1.095	Destabilizing	0.988	D	0.669	neutral	None	None	None	None	N
A/G	0.2386	likely_benign	0.298	benign	-1.586	Destabilizing	0.896	D	0.532	neutral	N	0.521522314	None	None	N
A/H	0.9716	likely_pathogenic	0.977	pathogenic	-1.825	Destabilizing	0.999	D	0.654	neutral	None	None	None	None	N
A/I	0.4911	ambiguous	0.5303	ambiguous	-0.42	Destabilizing	0.976	D	0.684	prob.neutral	None	None	None	None	N
A/K	0.9755	likely_pathogenic	0.9805	pathogenic	-1.599	Destabilizing	0.919	D	0.653	neutral	None	None	None	None	N
A/L	0.5056	ambiguous	0.5194	ambiguous	-0.42	Destabilizing	0.851	D	0.599	neutral	None	None	None	None	N
A/M	0.5723	likely_pathogenic	0.6279	pathogenic	-0.425	Destabilizing	0.999	D	0.65	neutral	None	None	None	None	N
A/N	0.8271	likely_pathogenic	0.8527	pathogenic	-1.534	Destabilizing	0.976	D	0.656	neutral	None	None	None	None	N
A/P	0.435	ambiguous	0.4351	ambiguous	-0.654	Destabilizing	0.011	N	0.399	neutral	N	0.485317582	None	None	N
A/Q	0.9272	likely_pathogenic	0.9348	pathogenic	-1.609	Destabilizing	0.988	D	0.687	prob.neutral	None	None	None	None	N
A/R	0.9618	likely_pathogenic	0.9647	pathogenic	-1.31	Destabilizing	0.988	D	0.672	neutral	None	None	None	None	N
A/S	0.1768	likely_benign	0.2083	benign	-1.867	Destabilizing	0.811	D	0.541	neutral	N	0.491640634	None	None	N
A/T	0.1193	likely_benign	0.158	benign	-1.728	Destabilizing	0.103	N	0.385	neutral	N	0.479140333	None	None	N
A/V	0.1849	likely_benign	0.2187	benign	-0.654	Destabilizing	0.811	D	0.571	neutral	N	0.503152746	None	None	N
A/W	0.9874	likely_pathogenic	0.9902	pathogenic	-1.611	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
A/Y	0.9596	likely_pathogenic	0.9683	pathogenic	-1.193	Destabilizing	0.996	D	0.666	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.