TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23913	71962;71963;71964	chr2:178574395;178574394;178574393	chr2:179439122;179439121;179439120
N2AB	22272	67039;67040;67041	chr2:178574395;178574394;178574393	chr2:179439122;179439121;179439120
N2A	21345	64258;64259;64260	chr2:178574395;178574394;178574393	chr2:179439122;179439121;179439120
N2B	14848	44767;44768;44769	chr2:178574395;178574394;178574393	chr2:179439122;179439121;179439120
Novex-1	14973	45142;45143;45144	chr2:178574395;178574394;178574393	chr2:179439122;179439121;179439120
Novex-2	15040	45343;45344;45345	chr2:178574395;178574394;178574393	chr2:179439122;179439121;179439120
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: Fn3-61
• Domain position: 88
• Structural Position: 121
• Q(SASA): 0.1962
• 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/N	rs1709335824	None	0.999	D	0.892	0.576	0.49676076625	gnomAD-4.0.0	1.59182E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8593E-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
S/A	0.4298	ambiguous	0.4657	ambiguous	-0.71	Destabilizing	0.998	D	0.854	deleterious	None	None	None	None	N
S/C	0.5379	ambiguous	0.5669	pathogenic	-0.737	Destabilizing	1.0	D	0.864	deleterious	D	0.560145081	None	None	N
S/D	0.9934	likely_pathogenic	0.9932	pathogenic	-1.321	Destabilizing	0.999	D	0.886	deleterious	None	None	None	None	N
S/E	0.9958	likely_pathogenic	0.9957	pathogenic	-1.225	Destabilizing	0.999	D	0.882	deleterious	None	None	None	None	N
S/F	0.9921	likely_pathogenic	0.9936	pathogenic	-0.486	Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
S/G	0.3074	likely_benign	0.3152	benign	-1.047	Destabilizing	0.999	D	0.864	deleterious	D	0.53459486	None	None	N
S/H	0.9914	likely_pathogenic	0.9918	pathogenic	-1.487	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
S/I	0.9823	likely_pathogenic	0.9832	pathogenic	0.11	Stabilizing	1.0	D	0.908	deleterious	D	0.577742357	None	None	N
S/K	0.9993	likely_pathogenic	0.9992	pathogenic	-0.958	Destabilizing	0.999	D	0.879	deleterious	None	None	None	None	N
S/L	0.9192	likely_pathogenic	0.9258	pathogenic	0.11	Stabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
S/M	0.9651	likely_pathogenic	0.9699	pathogenic	0.15	Stabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
S/N	0.9641	likely_pathogenic	0.963	pathogenic	-1.256	Destabilizing	0.999	D	0.892	deleterious	D	0.577488868	None	None	N
S/P	0.9902	likely_pathogenic	0.9914	pathogenic	-0.128	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
S/Q	0.9927	likely_pathogenic	0.9926	pathogenic	-1.215	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
S/R	0.9978	likely_pathogenic	0.9979	pathogenic	-1.023	Destabilizing	1.0	D	0.881	deleterious	D	0.558624144	None	None	N
S/T	0.5848	likely_pathogenic	0.5837	pathogenic	-1.025	Destabilizing	0.999	D	0.882	deleterious	D	0.537099621	None	None	N
S/V	0.9481	likely_pathogenic	0.9528	pathogenic	-0.128	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
S/W	0.994	likely_pathogenic	0.9947	pathogenic	-0.649	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
S/Y	0.9906	likely_pathogenic	0.9916	pathogenic	-0.318	Destabilizing	1.0	D	0.918	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.