TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14946	45061;45062;45063	chr2:178622747;178622746;178622745	chr2:179487474;179487473;179487472
N2AB	13305	40138;40139;40140	chr2:178622747;178622746;178622745	chr2:179487474;179487473;179487472
N2A	12378	37357;37358;37359	chr2:178622747;178622746;178622745	chr2:179487474;179487473;179487472
N2B	5881	17866;17867;17868	chr2:178622747;178622746;178622745	chr2:179487474;179487473;179487472
Novex-1	6006	18241;18242;18243	chr2:178622747;178622746;178622745	chr2:179487474;179487473;179487472
Novex-2	6073	18442;18443;18444	chr2:178622747;178622746;178622745	chr2:179487474;179487473;179487472
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-101
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.67
• 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/K	rs1291314776	0.031	0.002	N	0.146	0.126	0.298056030225	gnomAD-2.1.1	4.28E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.46E-06	0
R/K	rs1291314776	0.031	0.002	N	0.146	0.126	0.298056030225	gnomAD-4.0.0	4.13487E-06	None	None	None	None	N	None	3.01277E-05	0	None	0	0	None	0	0	4.51743E-06	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	0.4939	ambiguous	0.422	ambiguous	-0.077	Destabilizing	0.688	D	0.373	neutral	None	None	None	None	N
R/C	0.2519	likely_benign	0.2295	benign	-0.083	Destabilizing	0.998	D	0.43	neutral	None	None	None	None	N
R/D	0.7711	likely_pathogenic	0.7065	pathogenic	0.083	Stabilizing	0.842	D	0.441	neutral	None	None	None	None	N
R/E	0.4432	ambiguous	0.3616	ambiguous	0.201	Stabilizing	0.525	D	0.362	neutral	None	None	None	None	N
R/F	0.6397	likely_pathogenic	0.589	pathogenic	0.036	Stabilizing	0.991	D	0.449	neutral	None	None	None	None	N
R/G	0.372	ambiguous	0.2899	benign	-0.366	Destabilizing	0.801	D	0.427	neutral	N	0.513443363	None	None	N
R/H	0.0997	likely_benign	0.0957	benign	-0.89	Destabilizing	0.991	D	0.458	neutral	None	None	None	None	N
R/I	0.2968	likely_benign	0.2551	benign	0.678	Stabilizing	0.966	D	0.462	neutral	N	0.509887104	None	None	N
R/K	0.0976	likely_benign	0.0898	benign	-0.095	Destabilizing	0.002	N	0.146	neutral	N	0.362828874	None	None	N
R/L	0.2543	likely_benign	0.2238	benign	0.678	Stabilizing	0.842	D	0.427	neutral	None	None	None	None	N
R/M	0.3329	likely_benign	0.2818	benign	0.119	Stabilizing	0.991	D	0.453	neutral	None	None	None	None	N
R/N	0.5756	likely_pathogenic	0.5277	ambiguous	0.239	Stabilizing	0.842	D	0.365	neutral	None	None	None	None	N
R/P	0.8939	likely_pathogenic	0.8399	pathogenic	0.449	Stabilizing	0.915	D	0.477	neutral	None	None	None	None	N
R/Q	0.1155	likely_benign	0.1055	benign	0.184	Stabilizing	0.842	D	0.381	neutral	None	None	None	None	N
R/S	0.514	ambiguous	0.4415	ambiguous	-0.221	Destabilizing	0.625	D	0.395	neutral	N	0.495074694	None	None	N
R/T	0.2641	likely_benign	0.2131	benign	0.067	Stabilizing	0.801	D	0.422	neutral	N	0.482954944	None	None	N
R/V	0.3976	ambiguous	0.3568	ambiguous	0.449	Stabilizing	0.915	D	0.477	neutral	None	None	None	None	N
R/W	0.2846	likely_benign	0.2386	benign	0.144	Stabilizing	0.998	D	0.449	neutral	None	None	None	None	N
R/Y	0.488	ambiguous	0.4617	ambiguous	0.496	Stabilizing	0.991	D	0.455	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.