TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17677	53254;53255;53256	chr2:178607659;178607658;178607657	chr2:179472386;179472385;179472384
N2AB	16036	48331;48332;48333	chr2:178607659;178607658;178607657	chr2:179472386;179472385;179472384
N2A	15109	45550;45551;45552	chr2:178607659;178607658;178607657	chr2:179472386;179472385;179472384
N2B	8612	26059;26060;26061	chr2:178607659;178607658;178607657	chr2:179472386;179472385;179472384
Novex-1	8737	26434;26435;26436	chr2:178607659;178607658;178607657	chr2:179472386;179472385;179472384
Novex-2	8804	26635;26636;26637	chr2:178607659;178607658;178607657	chr2:179472386;179472385;179472384
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-113
• Domain position: 1
• Structural Position: 1
• Q(SASA): 1.0447
• Predicted PPI site: I

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/C	None	None	1.0	D	0.532	0.393	0.633926072375	gnomAD-4.0.0	1.59294E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43308E-05	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
S/A	0.107	likely_benign	0.1024	benign	-0.184	Destabilizing	0.973	D	0.522	neutral	N	0.508830316	None	None	I
S/C	0.2482	likely_benign	0.2535	benign	-0.698	Destabilizing	1.0	D	0.532	neutral	D	0.529843094	None	None	I
S/D	0.6325	likely_pathogenic	0.5989	pathogenic	-0.21	Destabilizing	0.996	D	0.532	neutral	None	None	None	None	I
S/E	0.6791	likely_pathogenic	0.663	pathogenic	-0.304	Destabilizing	0.996	D	0.533	neutral	None	None	None	None	I
S/F	0.4185	ambiguous	0.3784	ambiguous	-0.984	Destabilizing	0.999	D	0.545	neutral	D	0.529496377	None	None	I
S/G	0.1746	likely_benign	0.1616	benign	-0.195	Destabilizing	0.996	D	0.553	neutral	None	None	None	None	I
S/H	0.6121	likely_pathogenic	0.5989	pathogenic	-0.306	Destabilizing	1.0	D	0.526	neutral	None	None	None	None	I
S/I	0.4525	ambiguous	0.4426	ambiguous	-0.274	Destabilizing	1.0	D	0.548	neutral	None	None	None	None	I
S/K	0.8733	likely_pathogenic	0.8544	pathogenic	-0.485	Destabilizing	0.996	D	0.531	neutral	None	None	None	None	I
S/L	0.1709	likely_benign	0.1609	benign	-0.274	Destabilizing	0.999	D	0.495	neutral	None	None	None	None	I
S/M	0.2928	likely_benign	0.2841	benign	-0.513	Destabilizing	1.0	D	0.525	neutral	None	None	None	None	I
S/N	0.3178	likely_benign	0.2918	benign	-0.369	Destabilizing	0.999	D	0.537	neutral	None	None	None	None	I
S/P	0.7779	likely_pathogenic	0.72	pathogenic	-0.224	Destabilizing	0.217	N	0.371	neutral	D	0.528802944	None	None	I
S/Q	0.7054	likely_pathogenic	0.6954	pathogenic	-0.529	Destabilizing	1.0	D	0.531	neutral	None	None	None	None	I
S/R	0.8246	likely_pathogenic	0.7983	pathogenic	-0.175	Destabilizing	1.0	D	0.535	neutral	None	None	None	None	I
S/T	0.0899	likely_benign	0.0894	benign	-0.46	Destabilizing	0.994	D	0.549	neutral	D	0.528282869	None	None	I
S/V	0.3868	ambiguous	0.3779	ambiguous	-0.224	Destabilizing	0.999	D	0.525	neutral	None	None	None	None	I
S/W	0.5423	ambiguous	0.5201	ambiguous	-1.122	Destabilizing	1.0	D	0.648	neutral	None	None	None	None	I
S/Y	0.3862	ambiguous	0.3743	ambiguous	-0.792	Destabilizing	0.999	D	0.537	neutral	D	0.529669735	None	None	I

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.