TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9479	28660;28661;28662	chr2:178710662;178710661;178710660	chr2:179575389;179575388;179575387
N2AB	9162	27709;27710;27711	chr2:178710662;178710661;178710660	chr2:179575389;179575388;179575387
N2A	8235	24928;24929;24930	chr2:178710662;178710661;178710660	chr2:179575389;179575388;179575387
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-80
• Domain position: 83
• Structural Position: 168
• Q(SASA): 0.2241
• 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/C	None	None	0.983	None	0.531	0.513	0.675278370098	gnomAD-4.0.0	1.59464E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86048E-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	0.0896	likely_benign	0.0995	benign	-0.81	Destabilizing	0.007	N	0.181	neutral	None	None	None	None	N
S/C	0.1633	likely_benign	0.2371	benign	-0.356	Destabilizing	0.983	D	0.531	neutral	None	None	None	None	N
S/D	0.5656	likely_pathogenic	0.6253	pathogenic	0.257	Stabilizing	0.854	D	0.499	neutral	None	None	None	None	N
S/E	0.5737	likely_pathogenic	0.65	pathogenic	0.255	Stabilizing	0.742	D	0.489	neutral	None	None	None	None	N
S/F	0.151	likely_benign	0.1806	benign	-0.939	Destabilizing	0.015	N	0.457	neutral	None	None	None	None	N
S/G	0.1581	likely_benign	0.2065	benign	-1.057	Destabilizing	0.59	D	0.501	neutral	None	None	None	None	N
S/H	0.3526	ambiguous	0.4424	ambiguous	-1.368	Destabilizing	0.996	D	0.532	neutral	None	None	None	None	N
S/I	0.1577	likely_benign	0.1955	benign	-0.256	Destabilizing	0.59	D	0.541	neutral	None	None	None	None	N
S/K	0.6781	likely_pathogenic	0.7801	pathogenic	-0.52	Destabilizing	0.742	D	0.488	neutral	None	None	None	None	N
S/L	0.1164	likely_benign	0.1416	benign	-0.256	Destabilizing	0.009	N	0.42	neutral	None	None	None	None	N
S/M	0.2141	likely_benign	0.2743	benign	-0.054	Destabilizing	0.91	D	0.545	neutral	None	None	None	None	N
S/N	0.1885	likely_benign	0.2323	benign	-0.375	Destabilizing	0.854	D	0.512	neutral	None	None	None	None	N
S/P	0.8596	likely_pathogenic	0.9385	pathogenic	-0.407	Destabilizing	0.939	D	0.553	neutral	None	None	None	None	N
S/Q	0.5072	ambiguous	0.6109	pathogenic	-0.491	Destabilizing	0.953	D	0.502	neutral	None	None	None	None	N
S/R	0.5506	ambiguous	0.643	pathogenic	-0.429	Destabilizing	0.953	D	0.555	neutral	None	None	None	None	N
S/T	0.086	likely_benign	0.0951	benign	-0.481	Destabilizing	0.028	N	0.316	neutral	None	None	None	None	N
S/V	0.1799	likely_benign	0.2123	benign	-0.407	Destabilizing	0.037	N	0.466	neutral	None	None	None	None	N
S/W	0.3679	ambiguous	0.4533	ambiguous	-0.885	Destabilizing	0.996	D	0.641	neutral	None	None	None	None	N
S/Y	0.1612	likely_benign	0.2077	benign	-0.64	Destabilizing	0.792	D	0.591	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.