TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31925	95998;95999;96000	chr2:178544456;178544455;178544454	chr2:179409183;179409182;179409181
N2AB	30284	91075;91076;91077	chr2:178544456;178544455;178544454	chr2:179409183;179409182;179409181
N2A	29357	88294;88295;88296	chr2:178544456;178544455;178544454	chr2:179409183;179409182;179409181
N2B	22860	68803;68804;68805	chr2:178544456;178544455;178544454	chr2:179409183;179409182;179409181
Novex-1	22985	69178;69179;69180	chr2:178544456;178544455;178544454	chr2:179409183;179409182;179409181
Novex-2	23052	69379;69380;69381	chr2:178544456;178544455;178544454	chr2:179409183;179409182;179409181
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-121
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.1971
• 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
S/R	None	None	1.0	N	0.833	0.537	0.498896430806	gnomAD-4.0.0	6.84393E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65684E-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
S/A	0.1888	likely_benign	0.2116	benign	-0.447	Destabilizing	0.998	D	0.447	neutral	None	None	None	None	N
S/C	0.1764	likely_benign	0.1936	benign	-0.953	Destabilizing	1.0	D	0.789	deleterious	N	0.496271712	None	None	N
S/D	0.8639	likely_pathogenic	0.8467	pathogenic	-2.058	Highly Destabilizing	0.999	D	0.62	neutral	None	None	None	None	N
S/E	0.9125	likely_pathogenic	0.9066	pathogenic	-1.976	Destabilizing	0.999	D	0.6	neutral	None	None	None	None	N
S/F	0.5517	ambiguous	0.5123	ambiguous	-0.79	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
S/G	0.226	likely_benign	0.2476	benign	-0.694	Destabilizing	0.999	D	0.506	neutral	N	0.494181344	None	None	N
S/H	0.6398	likely_pathogenic	0.6238	pathogenic	-1.255	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
S/I	0.6997	likely_pathogenic	0.639	pathogenic	0.115	Stabilizing	1.0	D	0.843	deleterious	D	0.542760117	None	None	N
S/K	0.9507	likely_pathogenic	0.9492	pathogenic	-0.573	Destabilizing	0.999	D	0.601	neutral	None	None	None	None	N
S/L	0.3456	ambiguous	0.319	benign	0.115	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
S/M	0.445	ambiguous	0.4364	ambiguous	0.138	Stabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
S/N	0.4573	ambiguous	0.4537	ambiguous	-1.145	Destabilizing	0.999	D	0.601	neutral	N	0.482900717	None	None	N
S/P	0.9937	likely_pathogenic	0.9902	pathogenic	-0.04	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
S/Q	0.8312	likely_pathogenic	0.8292	pathogenic	-1.256	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
S/R	0.918	likely_pathogenic	0.9108	pathogenic	-0.57	Destabilizing	1.0	D	0.833	deleterious	N	0.499194547	None	None	N
S/T	0.1103	likely_benign	0.1087	benign	-0.773	Destabilizing	0.999	D	0.503	neutral	N	0.494282151	None	None	N
S/V	0.6013	likely_pathogenic	0.5661	pathogenic	-0.04	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
S/W	0.7629	likely_pathogenic	0.7036	pathogenic	-1.034	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
S/Y	0.5078	ambiguous	0.4535	ambiguous	-0.559	Destabilizing	1.0	D	0.859	deleterious	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.