TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28524	85795;85796;85797	chr2:178560562;178560561;178560560	chr2:179425289;179425288;179425287
N2AB	26883	80872;80873;80874	chr2:178560562;178560561;178560560	chr2:179425289;179425288;179425287
N2A	25956	78091;78092;78093	chr2:178560562;178560561;178560560	chr2:179425289;179425288;179425287
N2B	19459	58600;58601;58602	chr2:178560562;178560561;178560560	chr2:179425289;179425288;179425287
Novex-1	19584	58975;58976;58977	chr2:178560562;178560561;178560560	chr2:179425289;179425288;179425287
Novex-2	19651	59176;59177;59178	chr2:178560562;178560561;178560560	chr2:179425289;179425288;179425287
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-95
• Domain position: 75
• Structural Position: 107
• Q(SASA): 0.1795
• Predicted PPI site: I

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
R/I	None	None	1.0	D	0.823	0.623	0.865621390494	gnomAD-4.0.0	2.0534E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69873E-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
R/A	0.946	likely_pathogenic	0.953	pathogenic	-1.71	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	I
R/C	0.3484	ambiguous	0.3869	ambiguous	-1.664	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
R/D	0.994	likely_pathogenic	0.9946	pathogenic	-0.921	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
R/E	0.9204	likely_pathogenic	0.9275	pathogenic	-0.715	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	I
R/F	0.9709	likely_pathogenic	0.9722	pathogenic	-0.865	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
R/G	0.9147	likely_pathogenic	0.9238	pathogenic	-2.032	Highly Destabilizing	1.0	D	0.748	deleterious	D	0.547071623	None	None	I
R/H	0.271	likely_benign	0.2798	benign	-2.002	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
R/I	0.9057	likely_pathogenic	0.9128	pathogenic	-0.781	Destabilizing	1.0	D	0.823	deleterious	D	0.547071623	None	None	I
R/K	0.335	likely_benign	0.3931	ambiguous	-1.223	Destabilizing	0.997	D	0.669	neutral	N	0.491945483	None	None	I
R/L	0.8213	likely_pathogenic	0.8328	pathogenic	-0.781	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
R/M	0.8908	likely_pathogenic	0.9048	pathogenic	-1.349	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
R/N	0.9765	likely_pathogenic	0.98	pathogenic	-1.199	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
R/P	0.9975	likely_pathogenic	0.9981	pathogenic	-1.079	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	I
R/Q	0.29	likely_benign	0.3027	benign	-0.98	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	I
R/S	0.9567	likely_pathogenic	0.9581	pathogenic	-1.944	Destabilizing	1.0	D	0.741	deleterious	D	0.532419954	None	None	I
R/T	0.9203	likely_pathogenic	0.9299	pathogenic	-1.546	Destabilizing	1.0	D	0.751	deleterious	N	0.521824117	None	None	I
R/V	0.9282	likely_pathogenic	0.9362	pathogenic	-1.079	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
R/W	0.5928	likely_pathogenic	0.5685	pathogenic	-0.524	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
R/Y	0.9011	likely_pathogenic	0.9024	pathogenic	-0.355	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	I

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.