TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13724	41395;41396;41397	chr2:178636557;178636556;178636555	chr2:179501284;179501283;179501282
N2AB	12083	36472;36473;36474	chr2:178636557;178636556;178636555	chr2:179501284;179501283;179501282
N2A	11156	33691;33692;33693	chr2:178636557;178636556;178636555	chr2:179501284;179501283;179501282
N2B	4659	14200;14201;14202	chr2:178636557;178636556;178636555	chr2:179501284;179501283;179501282
Novex-1	4784	14575;14576;14577	chr2:178636557;178636556;178636555	chr2:179501284;179501283;179501282
Novex-2	4851	14776;14777;14778	chr2:178636557;178636556;178636555	chr2:179501284;179501283;179501282
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: Ig-87
• Domain position: 41
• Structural Position: 55
• Q(SASA): 0.2648
• 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/G	None	None	0.001	N	0.096	0.112	0.233785782151	gnomAD-4.0.0	6.84321E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99585E-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	0.1187	likely_benign	0.1339	benign	-0.274	Destabilizing	0.116	N	0.336	neutral	None	None	None	None	N
S/C	0.2291	likely_benign	0.2934	benign	-0.218	Destabilizing	0.975	D	0.395	neutral	D	0.545572946	None	None	N
S/D	0.5633	ambiguous	0.727	pathogenic	0.005	Stabilizing	0.241	N	0.335	neutral	None	None	None	None	N
S/E	0.6326	likely_pathogenic	0.7552	pathogenic	-0.103	Destabilizing	0.388	N	0.332	neutral	None	None	None	None	N
S/F	0.3847	ambiguous	0.5248	ambiguous	-0.943	Destabilizing	0.932	D	0.435	neutral	None	None	None	None	N
S/G	0.1172	likely_benign	0.1483	benign	-0.356	Destabilizing	0.001	N	0.096	neutral	N	0.477363063	None	None	N
S/H	0.4308	ambiguous	0.56	ambiguous	-0.821	Destabilizing	0.69	D	0.373	neutral	None	None	None	None	N
S/I	0.1994	likely_benign	0.2816	benign	-0.193	Destabilizing	0.627	D	0.445	neutral	N	0.494093795	None	None	N
S/K	0.7644	likely_pathogenic	0.8715	pathogenic	-0.447	Destabilizing	0.241	N	0.341	neutral	None	None	None	None	N
S/L	0.1894	likely_benign	0.2458	benign	-0.193	Destabilizing	0.388	N	0.427	neutral	None	None	None	None	N
S/M	0.2467	likely_benign	0.3118	benign	0.038	Stabilizing	0.981	D	0.371	neutral	None	None	None	None	N
S/N	0.113	likely_benign	0.166	benign	-0.137	Destabilizing	0.001	N	0.196	neutral	N	0.466112123	None	None	N
S/P	0.9671	likely_pathogenic	0.987	pathogenic	-0.193	Destabilizing	0.818	D	0.38	neutral	None	None	None	None	N
S/Q	0.5031	ambiguous	0.5888	pathogenic	-0.41	Destabilizing	0.69	D	0.377	neutral	None	None	None	None	N
S/R	0.6912	likely_pathogenic	0.8202	pathogenic	-0.19	Destabilizing	0.003	N	0.217	neutral	N	0.479314956	None	None	N
S/T	0.1057	likely_benign	0.1281	benign	-0.243	Destabilizing	0.006	N	0.205	neutral	N	0.445061651	None	None	N
S/V	0.2102	likely_benign	0.287	benign	-0.193	Destabilizing	0.388	N	0.429	neutral	None	None	None	None	N
S/W	0.6741	likely_pathogenic	0.8095	pathogenic	-0.983	Destabilizing	0.981	D	0.536	neutral	None	None	None	None	N
S/Y	0.357	ambiguous	0.5092	ambiguous	-0.692	Destabilizing	0.932	D	0.433	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.