TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22854	68785;68786;68787	chr2:178577866;178577865;178577864	chr2:179442593;179442592;179442591
N2AB	21213	63862;63863;63864	chr2:178577866;178577865;178577864	chr2:179442593;179442592;179442591
N2A	20286	61081;61082;61083	chr2:178577866;178577865;178577864	chr2:179442593;179442592;179442591
N2B	13789	41590;41591;41592	chr2:178577866;178577865;178577864	chr2:179442593;179442592;179442591
Novex-1	13914	41965;41966;41967	chr2:178577866;178577865;178577864	chr2:179442593;179442592;179442591
Novex-2	13981	42166;42167;42168	chr2:178577866;178577865;178577864	chr2:179442593;179442592;179442591
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-54
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.2437
• 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
T/R	rs2046780936	None	0.994	N	0.683	0.471	0.529510553188	gnomAD-4.0.0	1.64253E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.93962E-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
T/A	0.3492	ambiguous	0.3083	benign	-0.572	Destabilizing	0.958	D	0.412	neutral	N	0.494378246	None	None	N
T/C	0.7533	likely_pathogenic	0.7345	pathogenic	-0.617	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
T/D	0.7437	likely_pathogenic	0.7137	pathogenic	-1.498	Destabilizing	0.086	N	0.331	neutral	None	None	None	None	N
T/E	0.8089	likely_pathogenic	0.7945	pathogenic	-1.48	Destabilizing	0.938	D	0.536	neutral	None	None	None	None	N
T/F	0.782	likely_pathogenic	0.7527	pathogenic	-0.771	Destabilizing	0.998	D	0.747	deleterious	None	None	None	None	N
T/G	0.4073	ambiguous	0.3794	ambiguous	-0.828	Destabilizing	0.968	D	0.593	neutral	None	None	None	None	N
T/H	0.5891	likely_pathogenic	0.5646	pathogenic	-1.252	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
T/I	0.8739	likely_pathogenic	0.8438	pathogenic	0.021	Stabilizing	0.994	D	0.699	prob.neutral	D	0.537120896	None	None	N
T/K	0.6201	likely_pathogenic	0.5998	pathogenic	-0.838	Destabilizing	0.988	D	0.638	neutral	N	0.470589225	None	None	N
T/L	0.4358	ambiguous	0.393	ambiguous	0.021	Stabilizing	0.984	D	0.569	neutral	None	None	None	None	N
T/M	0.3152	likely_benign	0.2774	benign	0.399	Stabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
T/N	0.2829	likely_benign	0.2458	benign	-1.095	Destabilizing	0.982	D	0.605	neutral	None	None	None	None	N
T/P	0.8696	likely_pathogenic	0.8311	pathogenic	-0.145	Destabilizing	0.994	D	0.698	prob.neutral	D	0.53053753	None	None	N
T/Q	0.5411	ambiguous	0.5229	ambiguous	-1.324	Destabilizing	0.995	D	0.691	prob.neutral	None	None	None	None	N
T/R	0.5727	likely_pathogenic	0.5585	ambiguous	-0.549	Destabilizing	0.994	D	0.683	prob.neutral	N	0.494276114	None	None	N
T/S	0.1523	likely_benign	0.1335	benign	-1.128	Destabilizing	0.958	D	0.423	neutral	N	0.50178134	None	None	N
T/V	0.7419	likely_pathogenic	0.7021	pathogenic	-0.145	Destabilizing	0.984	D	0.507	neutral	None	None	None	None	N
T/W	0.9407	likely_pathogenic	0.9356	pathogenic	-0.835	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
T/Y	0.7823	likely_pathogenic	0.7687	pathogenic	-0.502	Destabilizing	0.998	D	0.745	deleterious	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.