TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25112	75559;75560;75561	chr2:178570798;178570797;178570796	chr2:179435525;179435524;179435523
N2AB	23471	70636;70637;70638	chr2:178570798;178570797;178570796	chr2:179435525;179435524;179435523
N2A	22544	67855;67856;67857	chr2:178570798;178570797;178570796	chr2:179435525;179435524;179435523
N2B	16047	48364;48365;48366	chr2:178570798;178570797;178570796	chr2:179435525;179435524;179435523
Novex-1	16172	48739;48740;48741	chr2:178570798;178570797;178570796	chr2:179435525;179435524;179435523
Novex-2	16239	48940;48941;48942	chr2:178570798;178570797;178570796	chr2:179435525;179435524;179435523
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-134
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.3179
• 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/T	rs984744354	-0.424	0.024	N	0.365	0.044	0.15556083564	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
S/T	rs984744354	-0.424	0.024	N	0.365	0.044	0.15556083564	gnomAD-4.0.0	1.59172E-06	None	None	None	None	N	None	0	2.28655E-05	None	0	0	None	0	0	0	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	0.1016	likely_benign	0.1037	benign	-0.553	Destabilizing	None	N	0.123	neutral	None	None	None	None	N
S/C	0.1322	likely_benign	0.1341	benign	-0.401	Destabilizing	0.828	D	0.361	neutral	D	0.524146485	None	None	N
S/D	0.4736	ambiguous	0.4143	ambiguous	0.288	Stabilizing	None	N	0.122	neutral	None	None	None	None	N
S/E	0.5352	ambiguous	0.4846	ambiguous	0.265	Stabilizing	None	N	0.148	neutral	None	None	None	None	N
S/F	0.2647	likely_benign	0.2826	benign	-0.929	Destabilizing	0.356	N	0.419	neutral	None	None	None	None	N
S/G	0.1566	likely_benign	0.1424	benign	-0.75	Destabilizing	0.024	N	0.342	neutral	D	0.52362641	None	None	N
S/H	0.3599	ambiguous	0.327	benign	-1.063	Destabilizing	0.356	N	0.353	neutral	None	None	None	None	N
S/I	0.2036	likely_benign	0.1888	benign	-0.149	Destabilizing	0.295	N	0.417	neutral	N	0.505387366	None	None	N
S/K	0.6652	likely_pathogenic	0.6191	pathogenic	-0.413	Destabilizing	0.016	N	0.325	neutral	None	None	None	None	N
S/L	0.1312	likely_benign	0.1397	benign	-0.149	Destabilizing	0.072	N	0.353	neutral	None	None	None	None	N
S/M	0.2277	likely_benign	0.222	benign	-0.149	Destabilizing	0.628	D	0.359	neutral	None	None	None	None	N
S/N	0.2148	likely_benign	0.191	benign	-0.33	Destabilizing	0.055	N	0.357	neutral	D	0.522066185	None	None	N
S/P	0.8425	likely_pathogenic	0.8551	pathogenic	-0.252	Destabilizing	0.136	N	0.376	neutral	None	None	None	None	N
S/Q	0.5091	ambiguous	0.4527	ambiguous	-0.427	Destabilizing	0.038	N	0.326	neutral	None	None	None	None	N
S/R	0.5659	likely_pathogenic	0.5181	ambiguous	-0.276	Destabilizing	None	N	0.371	neutral	N	0.485761456	None	None	N
S/T	0.1019	likely_benign	0.101	benign	-0.387	Destabilizing	0.024	N	0.365	neutral	N	0.473850951	None	None	N
S/V	0.2128	likely_benign	0.2109	benign	-0.252	Destabilizing	0.072	N	0.341	neutral	None	None	None	None	N
S/W	0.3942	ambiguous	0.4094	ambiguous	-0.951	Destabilizing	0.864	D	0.496	neutral	None	None	None	None	N
S/Y	0.229	likely_benign	0.236	benign	-0.649	Destabilizing	0.356	N	0.418	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.