Submissions for variant NM_177924.5(ASAH1):c.1004C>T (p.Thr335Met)

gnomAD frequency: 0.00158  dbSNP: rs147233112

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000853062	SCV000994992	uncertain significance	not provided	2022-01-27	criteria provided, single submitter	clinical testing	Reported as T351M due to the use of alternative nomenclature in an individual with Parkinson disease; however, additional clinical information was not provided and a second ASAH1 variant was not described (Robak et al., 2017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29140481)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000853062	SCV001098271	likely benign	not provided	2024-01-27	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001159010	SCV001320691	uncertain significance	Farber lipogranulomatosis	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Mayo Clinic Laboratories, Mayo Clinic	RCV000853062	SCV005409410	uncertain significance	not provided	2024-01-29	criteria provided, single submitter	clinical testing	BS1
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000853062	SCV001742040	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000853062	SCV001922322	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000853062	SCV001972640	uncertain significance	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004549916	SCV004762011	likely benign	ASAH1-related disorders	2022-02-11	no assertion criteria provided	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).