TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19279	58060;58061;58062	chr2:178595519;178595518;178595517	chr2:179460246;179460245;179460244
N2AB	17638	53137;53138;53139	chr2:178595519;178595518;178595517	chr2:179460246;179460245;179460244
N2A	16711	50356;50357;50358	chr2:178595519;178595518;178595517	chr2:179460246;179460245;179460244
N2B	10214	30865;30866;30867	chr2:178595519;178595518;178595517	chr2:179460246;179460245;179460244
Novex-1	10339	31240;31241;31242	chr2:178595519;178595518;178595517	chr2:179460246;179460245;179460244
Novex-2	10406	31441;31442;31443	chr2:178595519;178595518;178595517	chr2:179460246;179460245;179460244
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: Fn3-27
• Domain position: 97
• Structural Position: 131
• Q(SASA): 0.5379
• 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/G	None	None	0.651	N	0.425	0.198	0.517432700143	gnomAD-4.0.0	1.75052E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.13042E-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	0.4112	ambiguous	0.5694	pathogenic	0.017	Stabilizing	0.505	D	0.342	neutral	None	None	None	None	N
R/C	0.1966	likely_benign	0.2749	benign	-0.136	Destabilizing	0.995	D	0.348	neutral	None	None	None	None	N
R/D	0.6926	likely_pathogenic	0.8034	pathogenic	0.07	Stabilizing	0.712	D	0.373	neutral	None	None	None	None	N
R/E	0.314	likely_benign	0.4424	ambiguous	0.178	Stabilizing	0.338	N	0.333	neutral	None	None	None	None	N
R/F	0.6897	likely_pathogenic	0.8102	pathogenic	0.031	Stabilizing	0.946	D	0.43	neutral	None	None	None	None	N
R/G	0.3069	likely_benign	0.445	ambiguous	-0.243	Destabilizing	0.651	D	0.425	neutral	N	0.509659823	None	None	N
R/H	0.123	likely_benign	0.1578	benign	-0.733	Destabilizing	0.018	N	0.191	neutral	None	None	None	None	N
R/I	0.3686	ambiguous	0.489	ambiguous	0.683	Stabilizing	0.93	D	0.465	neutral	D	0.52662943	None	None	N
R/K	0.0924	likely_benign	0.112	benign	0.002	Stabilizing	0.01	N	0.155	neutral	N	0.415842797	None	None	N
R/L	0.3213	likely_benign	0.4436	ambiguous	0.683	Stabilizing	0.712	D	0.417	neutral	None	None	None	None	N
R/M	0.3156	likely_benign	0.4598	ambiguous	0.065	Stabilizing	0.982	D	0.39	neutral	None	None	None	None	N
R/N	0.5938	likely_pathogenic	0.7076	pathogenic	0.203	Stabilizing	0.712	D	0.315	neutral	None	None	None	None	N
R/P	0.8822	likely_pathogenic	0.8925	pathogenic	0.483	Stabilizing	0.946	D	0.443	neutral	None	None	None	None	N
R/Q	0.0934	likely_benign	0.1203	benign	0.169	Stabilizing	0.032	N	0.224	neutral	None	None	None	None	N
R/S	0.4297	ambiguous	0.586	pathogenic	-0.199	Destabilizing	0.651	D	0.397	neutral	N	0.503424497	None	None	N
R/T	0.1921	likely_benign	0.3084	benign	0.073	Stabilizing	0.651	D	0.378	neutral	N	0.495439732	None	None	N
R/V	0.3867	ambiguous	0.5136	ambiguous	0.483	Stabilizing	0.834	D	0.438	neutral	None	None	None	None	N
R/W	0.2542	likely_benign	0.3842	ambiguous	0.061	Stabilizing	0.995	D	0.395	neutral	None	None	None	None	N
R/Y	0.5186	ambiguous	0.6554	pathogenic	0.442	Stabilizing	0.897	D	0.467	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.