TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4972	15139;15140;15141	chr2:178735532;178735531;178735530	chr2:179600259;179600258;179600257
N2AB	4655	14188;14189;14190	chr2:178735532;178735531;178735530	chr2:179600259;179600258;179600257
N2A	3728	11407;11408;11409	chr2:178735532;178735531;178735530	chr2:179600259;179600258;179600257
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: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-32
• Domain position: 85
• Structural Position: 171
• Q(SASA): 0.5089
• 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/L	rs868769069	None	0.193	N	0.611	0.322	0.522023262976	gnomAD-4.0.0	6.94348E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.06462E-07	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	0.0781	likely_benign	0.0849	benign	-0.473	Destabilizing	0.006	N	0.233	neutral	N	0.399468892	None	None	N
S/C	0.1258	likely_benign	0.1234	benign	-0.315	Destabilizing	0.944	D	0.559	neutral	None	None	None	None	N
S/D	0.3121	likely_benign	0.415	ambiguous	-0.072	Destabilizing	0.241	N	0.52	neutral	None	None	None	None	N
S/E	0.3537	ambiguous	0.4449	ambiguous	-0.148	Destabilizing	0.008	N	0.221	neutral	None	None	None	None	N
S/F	0.1247	likely_benign	0.131	benign	-0.906	Destabilizing	0.818	D	0.639	neutral	None	None	None	None	N
S/G	0.1028	likely_benign	0.1212	benign	-0.629	Destabilizing	0.388	N	0.506	neutral	None	None	None	None	N
S/H	0.2564	likely_benign	0.3025	benign	-1.174	Destabilizing	0.981	D	0.575	neutral	None	None	None	None	N
S/I	0.1349	likely_benign	0.1581	benign	-0.183	Destabilizing	0.527	D	0.655	neutral	None	None	None	None	N
S/K	0.4228	ambiguous	0.5228	ambiguous	-0.626	Destabilizing	0.388	N	0.511	neutral	None	None	None	None	N
S/L	0.0755	likely_benign	0.0791	benign	-0.183	Destabilizing	0.193	N	0.611	neutral	N	0.505785461	None	None	N
S/M	0.1744	likely_benign	0.198	benign	0.131	Stabilizing	0.944	D	0.561	neutral	None	None	None	None	N
S/N	0.1287	likely_benign	0.1589	benign	-0.342	Destabilizing	0.388	N	0.561	neutral	None	None	None	None	N
S/P	0.2357	likely_benign	0.3009	benign	-0.249	Destabilizing	0.773	D	0.596	neutral	N	0.514833547	None	None	N
S/Q	0.3566	ambiguous	0.4281	ambiguous	-0.619	Destabilizing	0.69	D	0.56	neutral	None	None	None	None	N
S/R	0.3414	ambiguous	0.4184	ambiguous	-0.413	Destabilizing	0.69	D	0.595	neutral	None	None	None	None	N
S/T	0.0748	likely_benign	0.0841	benign	-0.435	Destabilizing	0.001	N	0.304	neutral	N	0.402405881	None	None	N
S/V	0.1424	likely_benign	0.1642	benign	-0.249	Destabilizing	0.241	N	0.623	neutral	None	None	None	None	N
S/W	0.2649	likely_benign	0.2812	benign	-0.877	Destabilizing	0.981	D	0.647	neutral	None	None	None	None	N
S/Y	0.1416	likely_benign	0.1493	benign	-0.621	Destabilizing	0.818	D	0.641	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.