TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30794	92605;92606;92607	chr2:178549246;178549245;178549244	chr2:179413973;179413972;179413971
N2AB	29153	87682;87683;87684	chr2:178549246;178549245;178549244	chr2:179413973;179413972;179413971
N2A	28226	84901;84902;84903	chr2:178549246;178549245;178549244	chr2:179413973;179413972;179413971
N2B	21729	65410;65411;65412	chr2:178549246;178549245;178549244	chr2:179413973;179413972;179413971
Novex-1	21854	65785;65786;65787	chr2:178549246;178549245;178549244	chr2:179413973;179413972;179413971
Novex-2	21921	65986;65987;65988	chr2:178549246;178549245;178549244	chr2:179413973;179413972;179413971
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-112
• Domain position: 76
• Structural Position: 107
• Q(SASA): 0.1116
• 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
H/R	rs773998423	-1.381	None	N	0.184	0.303	0.117506650769	gnomAD-2.1.1	8.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.77E-05	0
H/R	rs773998423	-1.381	None	N	0.184	0.303	0.117506650769	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
H/R	rs773998423	-1.381	None	N	0.184	0.303	0.117506650769	gnomAD-4.0.0	7.43576E-06	None	None	None	None	N	None	0	3.33444E-05	None	0	0	None	0	0	7.62797E-06	0	1.60113E-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
H/A	0.4599	ambiguous	0.4746	ambiguous	-1.851	Destabilizing	0.104	N	0.68	prob.neutral	None	None	None	None	N
H/C	0.1817	likely_benign	0.181	benign	-1.056	Destabilizing	0.958	D	0.765	deleterious	None	None	None	None	N
H/D	0.6681	likely_pathogenic	0.6972	pathogenic	-1.915	Destabilizing	0.175	N	0.666	neutral	N	0.437209786	None	None	N
H/E	0.5483	ambiguous	0.568	pathogenic	-1.717	Destabilizing	0.055	N	0.525	neutral	None	None	None	None	N
H/F	0.4387	ambiguous	0.4408	ambiguous	0.154	Stabilizing	0.667	D	0.743	deleterious	None	None	None	None	N
H/G	0.5851	likely_pathogenic	0.5812	pathogenic	-2.244	Highly Destabilizing	0.22	N	0.689	prob.neutral	None	None	None	None	N
H/I	0.4853	ambiguous	0.482	ambiguous	-0.673	Destabilizing	0.667	D	0.745	deleterious	None	None	None	None	N
H/K	0.3167	likely_benign	0.3275	benign	-1.185	Destabilizing	0.055	N	0.656	neutral	None	None	None	None	N
H/L	0.1759	likely_benign	0.1689	benign	-0.673	Destabilizing	0.175	N	0.694	prob.neutral	N	0.410428617	None	None	N
H/M	0.6144	likely_pathogenic	0.622	pathogenic	-0.888	Destabilizing	0.667	D	0.753	deleterious	None	None	None	None	N
H/N	0.2348	likely_benign	0.2472	benign	-1.873	Destabilizing	0.175	N	0.571	neutral	N	0.444231759	None	None	N
H/P	0.9142	likely_pathogenic	0.9281	pathogenic	-1.059	Destabilizing	0.602	D	0.743	deleterious	N	0.475074741	None	None	N
H/Q	0.1854	likely_benign	0.2076	benign	-1.453	Destabilizing	0.003	N	0.294	neutral	N	0.368021847	None	None	N
H/R	0.0851	likely_benign	0.0901	benign	-1.339	Destabilizing	None	N	0.184	neutral	N	0.208865264	None	None	N
H/S	0.3948	ambiguous	0.4116	ambiguous	-2.003	Highly Destabilizing	0.104	N	0.639	neutral	None	None	None	None	N
H/T	0.4496	ambiguous	0.4634	ambiguous	-1.698	Destabilizing	0.22	N	0.693	prob.neutral	None	None	None	None	N
H/V	0.4077	ambiguous	0.4064	ambiguous	-1.059	Destabilizing	0.22	N	0.726	prob.delet.	None	None	None	None	N
H/W	0.467	ambiguous	0.4734	ambiguous	0.679	Stabilizing	0.958	D	0.752	deleterious	None	None	None	None	N
H/Y	0.1565	likely_benign	0.1491	benign	0.438	Stabilizing	0.301	N	0.639	neutral	N	0.403617288	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.