TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29372	88339;88340;88341	chr2:178557040;178557039;178557038	chr2:179421767;179421766;179421765
N2AB	27731	83416;83417;83418	chr2:178557040;178557039;178557038	chr2:179421767;179421766;179421765
N2A	26804	80635;80636;80637	chr2:178557040;178557039;178557038	chr2:179421767;179421766;179421765
N2B	20307	61144;61145;61146	chr2:178557040;178557039;178557038	chr2:179421767;179421766;179421765
Novex-1	20432	61519;61520;61521	chr2:178557040;178557039;178557038	chr2:179421767;179421766;179421765
Novex-2	20499	61720;61721;61722	chr2:178557040;178557039;178557038	chr2:179421767;179421766;179421765
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-102
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.1172
• 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
V/A	None	None	0.517	D	0.579	0.487	0.723938039073	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
V/L	None	None	0.075	N	0.319	0.141	0.52540932818	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
V/A	0.7527	likely_pathogenic	0.688	pathogenic	-2.161	Highly Destabilizing	0.517	D	0.579	neutral	D	0.551681476	None	None	N
V/C	0.966	likely_pathogenic	0.9584	pathogenic	-1.357	Destabilizing	0.996	D	0.734	prob.delet.	None	None	None	None	N
V/D	0.9979	likely_pathogenic	0.9978	pathogenic	-3.118	Highly Destabilizing	0.983	D	0.878	deleterious	D	0.56379825	None	None	N
V/E	0.9918	likely_pathogenic	0.9908	pathogenic	-2.778	Highly Destabilizing	0.987	D	0.839	deleterious	None	None	None	None	N
V/F	0.8683	likely_pathogenic	0.8252	pathogenic	-1.251	Destabilizing	0.901	D	0.726	prob.delet.	D	0.563544761	None	None	N
V/G	0.9488	likely_pathogenic	0.9404	pathogenic	-2.781	Highly Destabilizing	0.949	D	0.859	deleterious	D	0.56379825	None	None	N
V/H	0.9977	likely_pathogenic	0.9972	pathogenic	-2.783	Highly Destabilizing	0.996	D	0.873	deleterious	None	None	None	None	N
V/I	0.085	likely_benign	0.078	benign	-0.341	Destabilizing	0.003	N	0.173	neutral	N	0.440525024	None	None	N
V/K	0.9933	likely_pathogenic	0.9932	pathogenic	-1.709	Destabilizing	0.961	D	0.839	deleterious	None	None	None	None	N
V/L	0.4667	ambiguous	0.4032	ambiguous	-0.341	Destabilizing	0.075	N	0.319	neutral	N	0.480978614	None	None	N
V/M	0.6121	likely_pathogenic	0.5408	ambiguous	-0.554	Destabilizing	0.923	D	0.632	neutral	None	None	None	None	N
V/N	0.9938	likely_pathogenic	0.9929	pathogenic	-2.499	Highly Destabilizing	0.987	D	0.888	deleterious	None	None	None	None	N
V/P	0.9749	likely_pathogenic	0.9697	pathogenic	-0.932	Destabilizing	0.987	D	0.849	deleterious	None	None	None	None	N
V/Q	0.9905	likely_pathogenic	0.9887	pathogenic	-2.061	Highly Destabilizing	0.987	D	0.873	deleterious	None	None	None	None	N
V/R	0.9863	likely_pathogenic	0.9854	pathogenic	-2.007	Highly Destabilizing	0.987	D	0.886	deleterious	None	None	None	None	N
V/S	0.9605	likely_pathogenic	0.9508	pathogenic	-2.939	Highly Destabilizing	0.961	D	0.805	deleterious	None	None	None	None	N
V/T	0.807	likely_pathogenic	0.7593	pathogenic	-2.427	Highly Destabilizing	0.775	D	0.608	neutral	None	None	None	None	N
V/W	0.9973	likely_pathogenic	0.9961	pathogenic	-1.771	Destabilizing	0.996	D	0.848	deleterious	None	None	None	None	N
V/Y	0.9919	likely_pathogenic	0.9893	pathogenic	-1.452	Destabilizing	0.961	D	0.725	prob.delet.	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.