TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22954	69085;69086;69087	chr2:178577475;178577474;178577473	chr2:179442202;179442201;179442200
N2AB	21313	64162;64163;64164	chr2:178577475;178577474;178577473	chr2:179442202;179442201;179442200
N2A	20386	61381;61382;61383	chr2:178577475;178577474;178577473	chr2:179442202;179442201;179442200
N2B	13889	41890;41891;41892	chr2:178577475;178577474;178577473	chr2:179442202;179442201;179442200
Novex-1	14014	42265;42266;42267	chr2:178577475;178577474;178577473	chr2:179442202;179442201;179442200
Novex-2	14081	42466;42467;42468	chr2:178577475;178577474;178577473	chr2:179442202;179442201;179442200
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-128
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.6392
• 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
D/N	None	None	0.967	N	0.651	0.339	0.326074293725	gnomAD-4.0.0	6.92941E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.09099E-07	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
D/A	0.1382	likely_benign	0.1268	benign	0.085	Stabilizing	0.892	D	0.602	neutral	N	0.515663075	None	None	N
D/C	0.5994	likely_pathogenic	0.5543	ambiguous	0.008	Stabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
D/E	0.1033	likely_benign	0.1013	benign	-0.356	Destabilizing	0.011	N	0.229	neutral	N	0.417152306	None	None	N
D/F	0.5945	likely_pathogenic	0.5363	ambiguous	-0.102	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
D/G	0.1221	likely_benign	0.109	benign	0.004	Stabilizing	0.892	D	0.653	neutral	N	0.520474249	None	None	N
D/H	0.2699	likely_benign	0.2254	benign	0.436	Stabilizing	0.995	D	0.705	prob.neutral	N	0.481400369	None	None	N
D/I	0.3738	ambiguous	0.3158	benign	0.223	Stabilizing	0.987	D	0.753	deleterious	None	None	None	None	N
D/K	0.277	likely_benign	0.2346	benign	0.52	Stabilizing	0.845	D	0.654	neutral	None	None	None	None	N
D/L	0.3795	ambiguous	0.3431	ambiguous	0.223	Stabilizing	0.975	D	0.745	deleterious	None	None	None	None	N
D/M	0.5537	ambiguous	0.4862	ambiguous	0.102	Stabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	N
D/N	0.0938	likely_benign	0.0852	benign	0.357	Stabilizing	0.967	D	0.651	neutral	N	0.482166577	None	None	N
D/P	0.5491	ambiguous	0.5202	ambiguous	0.195	Stabilizing	0.987	D	0.732	prob.delet.	None	None	None	None	N
D/Q	0.2602	likely_benign	0.2312	benign	0.338	Stabilizing	0.95	D	0.681	prob.neutral	None	None	None	None	N
D/R	0.3626	ambiguous	0.3063	benign	0.634	Stabilizing	0.975	D	0.717	prob.delet.	None	None	None	None	N
D/S	0.1148	likely_benign	0.1031	benign	0.274	Stabilizing	0.916	D	0.634	neutral	None	None	None	None	N
D/T	0.1906	likely_benign	0.1709	benign	0.343	Stabilizing	0.975	D	0.681	prob.neutral	None	None	None	None	N
D/V	0.2091	likely_benign	0.183	benign	0.195	Stabilizing	0.983	D	0.746	deleterious	N	0.485755235	None	None	N
D/W	0.8386	likely_pathogenic	0.8141	pathogenic	-0.105	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
D/Y	0.2245	likely_benign	0.1964	benign	0.112	Stabilizing	0.999	D	0.726	prob.delet.	N	0.493263653	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.