Submissions for variant NM_012463.4(ATP6V0A2):c.422G>T (p.Arg141Leu)

dbSNP: rs143509747

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000423155	SCV000533684	uncertain significance	not specified	2016-11-17	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the ATP6V0A2 gene. The R141L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R141L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In addition, this substitution occurs at a position that is conserved across species, and 2/3 in silico algorithms predict this variant is probably damaging to the protein structure/function. However, to our knowledge no studies have been performed to determine the functional effect of the R141L variant.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.
Eurofins Ntd Llc (ga)	RCV000729905	SCV000857603	uncertain significance	not provided	2017-11-02	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000763802	SCV000894716	uncertain significance	Cutis laxa with osteodystrophy; Wrinkly skin syndrome	2024-06-04	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001113218	SCV001270974	uncertain significance	Cutis laxa with osteodystrophy	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
CeGaT Center for Human Genetics Tuebingen	RCV000729905	SCV001748397	uncertain significance	not provided	2021-06-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001861625	SCV002317210	likely benign	ALG9 congenital disorder of glycosylation	2024-12-16	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000729905	SCV001744858	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000729905	SCV001967188	likely benign	not provided		no assertion criteria provided	clinical testing