TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28594	86005;86006;86007	chr2:178560352;178560351;178560350	chr2:179425079;179425078;179425077
N2AB	26953	81082;81083;81084	chr2:178560352;178560351;178560350	chr2:179425079;179425078;179425077
N2A	26026	78301;78302;78303	chr2:178560352;178560351;178560350	chr2:179425079;179425078;179425077
N2B	19529	58810;58811;58812	chr2:178560352;178560351;178560350	chr2:179425079;179425078;179425077
Novex-1	19654	59185;59186;59187	chr2:178560352;178560351;178560350	chr2:179425079;179425078;179425077
Novex-2	19721	59386;59387;59388	chr2:178560352;178560351;178560350	chr2:179425079;179425078;179425077
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: Fn3-96
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.2247
• 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	rs1703174198	None	0.117	N	0.34	0.134	0.126345400529	gnomAD-4.0.0	1.59153E-06	None	None	None	None	N	None	0	0	None	0	2.77608E-05	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	0.141	likely_benign	0.1293	benign	-0.386	Destabilizing	0.035	N	0.284	neutral	None	None	None	None	N
S/C	0.1449	likely_benign	0.1125	benign	-0.349	Destabilizing	0.915	D	0.315	neutral	N	0.516063672	None	None	N
S/D	0.8213	likely_pathogenic	0.7761	pathogenic	0.114	Stabilizing	0.149	N	0.304	neutral	None	None	None	None	N
S/E	0.9153	likely_pathogenic	0.8868	pathogenic	0.021	Stabilizing	0.262	N	0.338	neutral	None	None	None	None	N
S/F	0.5831	likely_pathogenic	0.5357	ambiguous	-0.909	Destabilizing	0.235	N	0.364	neutral	None	None	None	None	N
S/G	0.0667	likely_benign	0.0587	benign	-0.504	Destabilizing	None	N	0.13	neutral	N	0.4100819	None	None	N
S/H	0.6409	likely_pathogenic	0.5918	pathogenic	-0.973	Destabilizing	0.935	D	0.297	neutral	None	None	None	None	N
S/I	0.4166	ambiguous	0.3301	benign	-0.204	Destabilizing	0.484	N	0.368	neutral	N	0.497705927	None	None	N
S/K	0.95	likely_pathogenic	0.9333	pathogenic	-0.552	Destabilizing	0.149	N	0.331	neutral	None	None	None	None	N
S/L	0.2355	likely_benign	0.1992	benign	-0.204	Destabilizing	0.149	N	0.332	neutral	None	None	None	None	N
S/M	0.3767	ambiguous	0.3248	benign	0.012	Stabilizing	0.935	D	0.296	neutral	None	None	None	None	N
S/N	0.2977	likely_benign	0.2513	benign	-0.257	Destabilizing	0.117	N	0.345	neutral	N	0.513633129	None	None	N
S/P	0.8782	likely_pathogenic	0.8401	pathogenic	-0.236	Destabilizing	0.555	D	0.305	neutral	None	None	None	None	N
S/Q	0.8088	likely_pathogenic	0.7713	pathogenic	-0.525	Destabilizing	0.555	D	0.319	neutral	None	None	None	None	N
S/R	0.9096	likely_pathogenic	0.8859	pathogenic	-0.315	Destabilizing	0.484	N	0.31	neutral	N	0.516942793	None	None	N
S/T	0.1437	likely_benign	0.1286	benign	-0.382	Destabilizing	0.117	N	0.34	neutral	N	0.48142471	None	None	N
S/V	0.4115	ambiguous	0.3316	benign	-0.236	Destabilizing	0.262	N	0.367	neutral	None	None	None	None	N
S/W	0.7286	likely_pathogenic	0.6909	pathogenic	-0.896	Destabilizing	0.001	N	0.362	neutral	None	None	None	None	N
S/Y	0.4928	ambiguous	0.4542	ambiguous	-0.632	Destabilizing	0.235	N	0.365	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.