Submissions for variant NM_001164508.2(NEB):c.24520G>A (p.Ala8174Thr)

gnomAD frequency: 0.00018  dbSNP: rs199937246

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000725430	SCV000336883	uncertain significance	not provided	2015-11-13	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000697048	SCV000416818	uncertain significance	Nemaline myopathy 2	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.
GeneDx	RCV000725430	SCV000715134	likely benign	not provided	2020-10-15	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000697048	SCV000825638	benign	Nemaline myopathy 2	2024-10-24	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002519146	SCV003679184	uncertain significance	Inborn genetic diseases	2024-05-14	criteria provided, single submitter	clinical testing	The c.18952G>A (p.A6318T) alteration is located in exon 142 (coding exon 140) of the NEB gene. This alteration results from a G to A substitution at nucleotide position 18952, causing the alanine (A) at amino acid position 6318 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc.	RCV000697048	SCV001454435	uncertain significance	Nemaline myopathy 2	2020-01-17	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004547689	SCV004754614	likely benign	NEB-related disorder	2022-05-19	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).