Submissions for variant NM_005219.5(DIAPH1):c.1736G>A (p.Arg579His)

gnomAD frequency: 0.00147  dbSNP: rs182139018

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000724127	SCV000226486	uncertain significance	not provided	2014-11-04	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000221724	SCV000270116	likely benign	not specified	2017-12-14	criteria provided, single submitter	clinical testing	p.Arg579His in exon 16 of DIAPH1: This variant is not expected to have clinical significance because it has been identified in 0.17% (210/126644) of European c hromosomes and in 0.28% (71/25790) of Finnish chromosomes by the Genome Aggregat ion Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs182139018). In addition, computational prediction tools and conservation analyses suggest that the p.Arg579His variant may not impact the protein.
Invitae	RCV001082786	SCV000655950	likely benign	Autosomal dominant nonsyndromic hearing loss 1; Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001151711	SCV001312876	likely benign	Autosomal dominant nonsyndromic hearing loss 1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx	RCV000724127	SCV001765160	likely benign	not provided	2020-12-17	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000724127	SCV004157244	likely benign	not provided	2023-04-01	criteria provided, single submitter	clinical testing	DIAPH1: BP4
PreventionGenetics, part of Exact Sciences	RCV003917622	SCV004735533	likely benign	DIAPH1-related condition	2022-08-09	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).