TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8766	26521;26522;26523	chr2:178714478;178714477;178714476	chr2:179579205;179579204;179579203
N2AB	8449	25570;25571;25572	chr2:178714478;178714477;178714476	chr2:179579205;179579204;179579203
N2A	7522	22789;22790;22791	chr2:178714478;178714477;178714476	chr2:179579205;179579204;179579203
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-73
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.4642
• 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	rs1368458893	0.385	0.044	N	0.339	0.313	0.593771126905	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
S/L	rs1368458893	0.385	0.044	N	0.339	0.313	0.593771126905	gnomAD-4.0.0	1.5918E-06	None	None	None	None	N	None	0	2.28739E-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	0.0841	likely_benign	0.0946	benign	-0.401	Destabilizing	0.106	N	0.369	neutral	N	0.499192363	None	None	N
S/C	0.1972	likely_benign	0.2471	benign	-0.391	Destabilizing	0.998	D	0.523	neutral	None	None	None	None	N
S/D	0.406	ambiguous	0.4912	ambiguous	0.023	Stabilizing	0.913	D	0.468	neutral	None	None	None	None	N
S/E	0.5152	ambiguous	0.5762	pathogenic	0.074	Stabilizing	0.936	D	0.433	neutral	None	None	None	None	N
S/F	0.1564	likely_benign	0.1946	benign	-0.613	Destabilizing	0.985	D	0.635	neutral	None	None	None	None	N
S/G	0.1477	likely_benign	0.1891	benign	-0.673	Destabilizing	0.951	D	0.447	neutral	None	None	None	None	N
S/H	0.3531	ambiguous	0.3924	ambiguous	-1.034	Destabilizing	0.999	D	0.527	neutral	None	None	None	None	N
S/I	0.2082	likely_benign	0.2596	benign	0.218	Stabilizing	0.906	D	0.579	neutral	None	None	None	None	N
S/K	0.6917	likely_pathogenic	0.7494	pathogenic	-0.348	Destabilizing	0.951	D	0.418	neutral	None	None	None	None	N
S/L	0.1051	likely_benign	0.1263	benign	0.218	Stabilizing	0.044	N	0.339	neutral	N	0.505802182	None	None	N
S/M	0.2218	likely_benign	0.2458	benign	0.056	Stabilizing	0.985	D	0.559	neutral	None	None	None	None	N
S/N	0.1877	likely_benign	0.2391	benign	-0.533	Destabilizing	0.551	D	0.488	neutral	None	None	None	None	N
S/P	0.604	likely_pathogenic	0.7734	pathogenic	0.047	Stabilizing	0.988	D	0.588	neutral	N	0.521450902	None	None	N
S/Q	0.5279	ambiguous	0.5697	pathogenic	-0.479	Destabilizing	0.998	D	0.513	neutral	None	None	None	None	N
S/R	0.5931	likely_pathogenic	0.6677	pathogenic	-0.398	Destabilizing	0.993	D	0.589	neutral	None	None	None	None	N
S/T	0.0828	likely_benign	0.0895	benign	-0.447	Destabilizing	0.003	N	0.169	neutral	N	0.459351219	None	None	N
S/V	0.196	likely_benign	0.2307	benign	0.047	Stabilizing	0.783	D	0.545	neutral	None	None	None	None	N
S/W	0.3132	likely_benign	0.3988	ambiguous	-0.746	Destabilizing	0.999	D	0.621	neutral	None	None	None	None	N
S/Y	0.1496	likely_benign	0.1804	benign	-0.367	Destabilizing	0.998	D	0.627	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.